Viruses

38 pages, 3811 KB

Open AccessReview

Chalcones as a Versatile Antiviral Scaffold: Molecular Targets, ADMET Profiles, and Translational Challenges

by Alvaro Luiz Helena, Patrick Rômbola Ozanique, Kevin Henrique Souza Lima, Wellington Negri Tondato, Victor Yukio Ichikawa Baio, Otávio Henrique Locateli Soares and Luis Octávio Regasini

Viruses 2026, 18(7), 806; https://doi.org/10.3390/v18070806 - 22 Jul 2026

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Abstract

Chalcones are naturally occurring open-chain flavonoids widely distributed in plants and recognized for their broad spectrum of pharmacological activities. Their versatile scaffold allows for extensive structural modifications, leading to a diverse range of natural and synthetic derivatives with notable biological potential. In the [...] Read more.

Chalcones are naturally occurring open-chain flavonoids widely distributed in plants and recognized for their broad spectrum of pharmacological activities. Their versatile scaffold allows for extensive structural modifications, leading to a diverse range of natural and synthetic derivatives with notable biological potential. In the context of viral infections, chalcones have demonstrated remarkable efficacy against a variety of human pathogens, including dengue virus, HIV, HCV, influenza A, SARS-CoV-2, and other emerging viruses. Beyond human health, several chalcones have shown potent activity against plant viruses such as tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV), and animal viruses including porcine reproductive and respiratory syndrome virus (PRRSV) and mammalian reovirus (MRV), underscoring their broad antiviral spectrum. These compounds act through multiple mechanisms, including the inhibition of viral enzymes (e.g., proteases, polymerases, and integrases), interference with viral entry and replication, and the modulation of host-related pathways. Recent advances in molecular docking, structure–activity relationship (SAR) studies, and synthetic optimization have further highlighted chalcones as a promising scaffold for antiviral drug discovery. Accordingly, this review summarizes and categorizes antiviral chalcones reported over the last two decades, emphasizing and critically discussing their molecular targets, mechanisms of action, and pharmacological potential as lead compounds. It also provides a comparative perspective on their pharmacological relevance by correlating their activities against standard therapeutic agents and reference inhibitors. Furthermore, the most recurrent viral targets were critically discussed regarding their conservation, expected genetic barriers to resistance, and the global SAR trends identified for the corresponding antiviral chalcones. Finally, in silico ADMET profiling of the most promising naturally occurring chalcones was performed to evaluate their drug-likeness and pharmacokinetic properties, offering guidance for future structural optimization and translational development. Collectively, these findings highlight the chalcone scaffold as a versatile platform for the development of novel antiviral agents targeting diverse viral and host pathways. Full article

(This article belongs to the Special Issue Natural, Semisynthetic, and Synthetic Antiviral Drugs: Combating Emerging and Re-Emerging Viral Threats)

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22 pages, 1338 KB

Open AccessArticle

Association of ABO/Rh Blood Groups and ABO Gene Variants rs8176746 and rs495828 with COVID-19 Severity Among Egyptian Patients

by Marwa H. Elnagdy, Alshimaa Magdy, Ahmed Hazem El-Nagdy, Eman Ali Elkordy, Ahmed E. Taha, Atef Elmougy, Mohamed Ayed Rashwan, Basil Mohammed Alomair, Anas Adi, Waleed Eldars, Mohamed Elgamal, Mohamed Ahmed Noureldin, Mayada Sabry Zeid and Ali Sobh

Viruses 2026, 18(7), 805; https://doi.org/10.3390/v18070805 - 22 Jul 2026

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Abstract

The link between ABO/Rh blood groups and COVID-19 severity remains a topic of debate. We aimed to investigate the role ABO/Rh blood groups, rs8176746 and rs495828 single nucleotide polymorphisms (SNPs), in COVID-19 severity among COVID-19 patients in Mansoura City, Egypt. A total of [...] Read more.

The link between ABO/Rh blood groups and COVID-19 severity remains a topic of debate. We aimed to investigate the role ABO/Rh blood groups, rs8176746 and rs495828 single nucleotide polymorphisms (SNPs), in COVID-19 severity among COVID-19 patients in Mansoura City, Egypt. A total of 306 Egyptian patients were included in this cross-sectional study. They were grouped into 86 cases with non-severe infection and 220 with severe infection according to clinical, laboratory, and radiological findings. ABO/Rh blood groups were confirmed. A TaqMan real-time PCR SNP genotyping assay was used to examine the allelic discrimination of rs8176746 and rs495828 SNPs. Older age, male gender, and the presence of comorbidities were associated with severe COVID-19. AB blood group was significantly associated with a protective effect against severe COVID-19 (p = 0.029) in the unadjusted analysis. There was no statistically significant association between Rh type and disease severity. GT genotype was significantly associated with a higher frequency of AB blood groups in both rs8176746 and rs495828 (p < 0.001). However, there was no statistically significant association between the studied SNPs and COVID-19 severity. After adjusting for age, gender, and the presence of comorbidities, the protective effect of the AB blood group with severe COVID-19 did not remain significant. No association was observed between Rh type rs8176746 and rs495828 SNPs and COVID-19 severity. The impact of ABO/Rh blood types and related SNPs on COVID-19 severity can vary by the ethnic group and population being studied. This diversity emphasizes the need for specialized research approaches to better understand the demographic, clinical, and genetic factors that lead to variations in COVID-19 outcomes among various groups. Full article

(This article belongs to the Section Coronaviruses)

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35 pages, 3238 KB

Open AccessReview

Drug Repurposing as a Broad-Spectrum Strategy Against Coronaviruses: Frontiers in Mechanisms and Clinical Translation

by Shuai Du, Yue Wang, Chao Liu, Yiming Han, Rui Zong, Shen Wang, Wenjuan Du, Linyang Yu and Yongtao Li

Viruses 2026, 18(7), 804; https://doi.org/10.3390/v18070804 - 21 Jul 2026

Viewed by 730

Abstract

Coronaviruses (family Coronaviridae) are enveloped, positive-sense, single-stranded RNA viruses with broad host adaptability. They transmit across species among humans, livestock, companion animals, and wildlife, eliciting a disease spectrum ranging from mild respiratory and gastrointestinal symptoms to fatal multi-organ failure, thereby posing significant [...] Read more.

Coronaviruses (family Coronaviridae) are enveloped, positive-sense, single-stranded RNA viruses with broad host adaptability. They transmit across species among humans, livestock, companion animals, and wildlife, eliciting a disease spectrum ranging from mild respiratory and gastrointestinal symptoms to fatal multi-organ failure, thereby posing significant challenges to global health. In this context, drug repurposing has emerged as a practical strategy for rapidly identifying broad-spectrum antivirals against emerging and re-emerging coronaviruses. Using coronaviruses as a paradigm, this review systematically summarizes research advances and mechanistic insights into the repurposing of existing drugs against coronaviruses. Simultaneously, we dissect core challenges including species-specific pharmacokinetic disparities, insufficient inter-genera conservation of viral targets, and systemic barriers between human and veterinary drug regulatory frameworks and propose innovative solutions encompassing AI-driven cross-species drug prediction, next-generation cross-species infection models, and a “human-veterinary dual-track” collaborative research and development system. Collectively, this review highlights the promise of drug repurposing as a broad-spectrum antiviral strategy and provides a translational perspective for the development of cross-species anti-coronavirus therapeutics. Full article

(This article belongs to the Special Issue Broad-Spectrum Antiviral Strategies Against Emerging and Re-Emerging Viral Diseases)

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33 pages, 21367 KB

Open AccessArticle

Structural Prediction and Antigenic Characterization of Recombinant Nucleocapsid Protein (p14) of Small Ruminant Lentivirus

by María Azucena Castañeda-Montes, José Luis Cerriteño-Sánchez, Julieta Sandra Cuevas-Romero, Francisco Jesus Castañeda-Montes, Dalia González-Esparragoza, Lucero de María Ávila-De la Vega and Hugo Ramírez-Álvarez

Viruses 2026, 18(7), 803; https://doi.org/10.3390/v18070803 - 21 Jul 2026

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Abstract

Small ruminant lentivirus (SRLV) infects goats and sheep of all breeds and ages worldwide. There are no current records regarding the three-dimensional structure or antigenic capacity of the nucleocapsid protein p14 of FESC-752 Mexican strain. The antigenic structure of p14 protein of a [...] Read more.

Small ruminant lentivirus (SRLV) infects goats and sheep of all breeds and ages worldwide. There are no current records regarding the three-dimensional structure or antigenic capacity of the nucleocapsid protein p14 of FESC-752 Mexican strain. The antigenic structure of p14 protein of a B1 genotype was predicted. cDNA from FESC-752 was used to overexpress the recombinant SRLV-rp14 protein. Then, its antigenicity was verified in vitro by evaluating plasma samples from goats and sheep naturally infected with SRLV. Antigenicity prediction showed a “horseshoe”-type structure shared by different lentiviruses and five epitopes distributed throughout the p14 surface regions where they coincide suggesting conserved epitopes in the zinc-finger structures of the nucleoproteins of the SRLV, Human Immunodeficiency Virus (HIV-1), and Feline Immunodeficiency virus (FIV) retroviruses. Multi-species molecular docking showed a notable structural convergence where caprine, bovine, murine, and human immunoglobulins target a predictive 23 amino acid epitope (residues 41–64) within the core zinc-finger region. Furthermore, CABS docking simulations predicted that p14-derived peptides preferentially bind within the antigen-presenting cleft of both caprine and bovine major histocompatibility complex class I (MHC-I) molecules. The stability of these immunological complexes is mediated by dense networks of hydrophobic interactions and highly conserved aromatic anchoring residues. Antigenicity analysis revealed that 78.7% of samples from naturally infected goats showed immunoreactivity toward SRLV-rp14 and the predictive evidence that p14 can simultaneously stimulate both humoral and cellular pathways makes it a strategic candidate for the design of next-generation vaccines aimed at controlling lentiviruses in small ruminants. Full article

(This article belongs to the Special Issue Viral Diseases of Sheep and Goats)

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16 pages, 8607 KB

Open AccessArticle

Toxic Relationships: Characterization of a Putative Virally Encoded Toxin in the Thermophilic Archaeal Fusellovirus SSV1

by Jonathan C. Abshier, Patrizia L. Alpapara, Guasåli Tomokane and Kenneth M. Stedman

Viruses 2026, 18(7), 802; https://doi.org/10.3390/v18070802 - 21 Jul 2026

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Abstract

Mechanisms for the maintenance of chronic viruses are poorly understood, particularly for archaeal viruses. Here, we identify the product of Sulfolobus spindle-shaped virus 1 (SSV1) ORF a291 as a putative virally encoded toxin required for growth inhibition but dispensable for viral replication and [...] Read more.

Mechanisms for the maintenance of chronic viruses are poorly understood, particularly for archaeal viruses. Here, we identify the product of Sulfolobus spindle-shaped virus 1 (SSV1) ORF a291 as a putative virally encoded toxin required for growth inhibition but dispensable for viral replication and virion production. Viruses lacking ORF a291 replicated their genomes and formed morphologically normal spindle-shaped particles, yet failed to inhibit the growth of uninfected Saccharolobus solfataricus. Substitution of residues at a predicted N-terminal signal peptide cleavage site abolished growth suppression without affecting replication, suggesting that secretion is essential for toxin function. Despite primary sequence divergence among fusellovirus toxin candidates, analysis of protein structure predictions revealed a conserved hydrolase-like fold across SSV1, SSV9 and SSV10 toxins. These findings demonstrate functional separation of viral replication and host growth suppression and support a model in which chronic archaeal viruses modulate host competition through antagonistic factors. This work expands the known diversity of putative viral toxins and suggests that fuselloviruses employ conserved strategies to promote persistence in extreme environments. Full article

(This article belongs to the Special Issue Viruses in Extreme Environments)

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23 pages, 9384 KB

Open AccessArticle

A Viral Long Non-Coding RNA Modulates Viral RNA Silencing Suppressor and DCL4-Associated DRB4 Protein Interaction

by Amélie Janzam, Lucie Bellott, Johana Chicher, Philippe Hammann, Camille Kempff, Line Jambois, Kamal Hleibieh, Fabrice Michel, Véronique Ziegler-Graff and David Gilmer

Viruses 2026, 18(7), 801; https://doi.org/10.3390/v18070801 - 20 Jul 2026

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Abstract

The expression of the BNYVV silencing suppressor (VSR) p14 protein, together with the production of a viral non-coding RNA (ncRNA3), affects the long-distance movement on natural host Beta species. Through immunoprecipitation of Flag-p14 and expression of TurboID-p14 coupled to mass spectrometry, we identified [...] Read more.

The expression of the BNYVV silencing suppressor (VSR) p14 protein, together with the production of a viral non-coding RNA (ncRNA3), affects the long-distance movement on natural host Beta species. Through immunoprecipitation of Flag-p14 and expression of TurboID-p14 coupled to mass spectrometry, we identified several potential p14 cellular partners. These include proteins related to RNA metabolism, proteasome activation, and notably, SGS3—a key player in the siRNA transitivity pathway—and DRB4, the DCL4 cofactor described in A. thaliana silencing pathways. The interaction between p14 and DRB4 was specifically retrieved with the hypomorphic p14BA2 VSR mutant in nucleoli and was disrupted in the presence of ncRNA3, a condition that allows the viral mutant to move long distances. Subcellular fractionation of infected tissues revealed that ncRNA3 accumulates in the nucleus through its interaction with p14, while genomic RNA3 remains cytoplasmic. Our results suggest that a specific viral RNA is targeted to the nucleus to participate in silencing suppression function by destabilizing the p14-DRB4 complex. Moreover, the interaction between p14 and SGS3 provides a mechanistic explanation of the role of this VSR in silencing transitivity. Full article

(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)

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29 pages, 2822 KB

Open AccessReview

Opportunistic CNS Viral Infections in Immunocompromised Patients

by Adriana A. M. Giuliani and Nancy Law

Viruses 2026, 18(7), 800; https://doi.org/10.3390/v18070800 - 20 Jul 2026

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Abstract

Immunocompromised patients face increased morbidity and mortality from central nervous system (CNS) opportunistic viral infections, with risk level driven by specific immune defects. While our diagnostic capacity expands, immunocompromised patients may present atypically or with mild symptoms, delaying or complicating diagnosis. Treatment options [...] Read more.

Immunocompromised patients face increased morbidity and mortality from central nervous system (CNS) opportunistic viral infections, with risk level driven by specific immune defects. While our diagnostic capacity expands, immunocompromised patients may present atypically or with mild symptoms, delaying or complicating diagnosis. Treatment options are often limited, although novel agents show promise. This review discusses why immunocompromised patients carry higher immunologic risk and how certain viral classes display neurotropism to invade the CNS. We outline the utility and limitations of current and emerging diagnostic strategies. We discuss specific opportunistic viral pathogens, denoting specific epidemiology or pathogenesis, clinical presentation, diagnostic findings, and treatment and prevention methods. While there still remain knowledge and treatment gaps, advancements in diagnostics and understanding of pathogens have begun to improve outcomes. Full article

(This article belongs to the Special Issue Opportunistic Viral Infections, 3rd Edition)

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14 pages, 12865 KB

Open AccessArticle

Detection of H5N1 HPAIV Clade 2.3.4.4b Avian Influenza Virus in Backyard Chickens in Costa Rica

by Bernal León, Hebleen Brenes, Nidia S. Trovao, Olga Aguilar, Fabián Carvajal, Idania Chacón, Guisella Chaves, Mónica Guzmán, Claudio Soto-Garita, Estela Cordero, Francisco Duarte-Martínez, Trushar Jeevan, Richard Webby, Adam Rubrum, Randall Arguedas and Ronaldo Chaves

Viruses 2026, 18(7), 799; https://doi.org/10.3390/v18070799 - 20 Jul 2026

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Abstract

Influenza A virus is a segmented, negative-sense RNA virus. Since the early 2020s, H5 clade 2.3.4.4b viruses have spread widely across Europe, Africa, and Asia, affecting wild birds and poultry. Costa Rica reported its first H5 clade 2.3.4.4b avian influenza virus (AIV) case [...] Read more.

Influenza A virus is a segmented, negative-sense RNA virus. Since the early 2020s, H5 clade 2.3.4.4b viruses have spread widely across Europe, Africa, and Asia, affecting wild birds and poultry. Costa Rica reported its first H5 clade 2.3.4.4b avian influenza virus (AIV) case on 19 January 2023. This study describes an outbreak in backyard chickens and ducks. Initial serum samples collected on 24 January showed three chickens negative for AIV, while one duck tested positive by ELISA and agar gel immunodiffusion (AGID). During a second visit on 27 January, three of four chicken sera collected tested positive by ELISA and AGID. Tissue samples were positive for influenza A by qRT-PCR. Next-generation sequencing recovered five of the eight viral genomic segments, and the hemagglutinin cleavage site sequence (REKRRKR↓G) confirmed a highly pathogenic avian influenza virus (HPAIV) H5 strain. The samples were submitted to the National Veterinary Services Laboratories for confirmation. Serological testing showed reactivity to North American low pathogenic H5 antigens, and qRT-PCR amplified influenza A and N1 genes. Virus isolation and next-generation sequencing (NGS) of all eight viral genome segments were successfully performed at the WHO Collaborating Centre at St. Jude Children’s Research Hospital (SJCRH). Full article

(This article belongs to the Special Issue Antigenic Drift in Respiratory Viruses)

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17 pages, 11080 KB

Open AccessArticle

Identification and Characterization of a Novel Luteovirus Infecting Hosta ventricosa Plants

by Liyan Li, Lele Chen, Tongkun Guo, Li Xie, Shuai Fu and Jianxiang Wu

Viruses 2026, 18(7), 798; https://doi.org/10.3390/v18070798 - 20 Jul 2026

Viewed by 368

Abstract

Hosta ventricosa, also known as blue plantain lily, is an important traditional herbal medicinal and ornamental plant in China. Prior to this study, no virus has been reported to infect H. ventricosa plants. Based on RNA-seq, transmission electron microscopy, and RT-PCR analyses, [...] Read more.

Hosta ventricosa, also known as blue plantain lily, is an important traditional herbal medicinal and ornamental plant in China. Prior to this study, no virus has been reported to infect H. ventricosa plants. Based on RNA-seq, transmission electron microscopy, and RT-PCR analyses, we have demonstrated that the H. ventricosa plant showing leaf chlorosis, mottle, mosaic, and crinkling symptoms was co-infected with hosta virus X (HVX) and a novel luteovirus, which we tentatively named hosta ventricosa luteovirus (HVLV). The genome of HVLV is a 5723 nt long, positive-sense, and single-stranded RNA with seven open reading frames (ORFs). Phylogenetic analysis based on the amino acid (aa) sequence of the viral RNA-dependent RNA polymerase (RdRp) revealed that HVLV is clustered within the genus Luteovirus. The HVLV RdRp shares 9.75–45.17% aa sequence identity with the 14 closely related luteoviruses. The P1–2 and P3–5 proteins of HVLV were identified as potential viral pathogenicity determinants through the PVX heterologous expression in Nicotiana benthamiana plants. Moreover, P2, P5 and P3–5 proteins of HVLV have been found to exhibit RNA silencing suppression activities. Additionally, we have successfully constructed an infectious cDNA clone of HVLV and uncovered that this infectious cDNA clone can infect N. benthamiana plants through agroinfiltration. These findings have expanded our understanding of luteoviruses and their host range. Full article

(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)

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20 pages, 3249 KB

Open AccessReview

The Dicistronic Nature of Picornavirus Genomes? Diverse Translation Mechanisms Enable the Expression of Accessory Proteins from Alternate Open Reading Frames

by Christopher U. T. Hellen

Viruses 2026, 18(7), 797; https://doi.org/10.3390/v18070797 - 20 Jul 2026

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Abstract

Members of the Picornaviridae family of viruses have single-stranded positive-sense RNA genomes, and are conventionally considered to contain a single open reading frame (ORF) preceded by a long 5′ untranslated region (UTR). The 5′UTR contains an internal ribosomal entry site (IRES) that mediates [...] Read more.

Members of the Picornaviridae family of viruses have single-stranded positive-sense RNA genomes, and are conventionally considered to contain a single open reading frame (ORF) preceded by a long 5′ untranslated region (UTR). The 5′UTR contains an internal ribosomal entry site (IRES) that mediates end-independent initiation of translation of ORF1, resulting in synthesis of a polyprotein that is proteolytically processed to yield the individual structural and nonstructural proteins. However, recent studies indicate that the dogma that picornavirus genomes contain a single ORF (ORF1) is an oversimplification, and that members of many picornavirus genera contain an additional ORF that is translated to yield an accessory protein that may influence pathogenicity and tissue specificity. This review summarizes the structural organization of picornavirus genomes that contain a second ORF. Most commonly, these ORFs overlap the 5′-end of ORF1, but they may also be wholly distinct from ORF1 or located entirely within it in a different reading frame. Ribosomal access to these alternate ORFs has been shown or is hypothesized to depend on a remarkable variety of non-canonical translation mechanisms, including ribosomal recruitment by a second IRES, leaky scanning after IRES-mediated internal ribosomal entry, cap-independent initiation, frame-shifting and termination–reinitiation. Full article

(This article belongs to the Special Issue Viral Strategies and Cellular Countermeasures That Regulate mRNA Access to the Translation Apparatus: 2nd Edition)

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1 pages, 129 KB

Open AccessCorrection

Correction: Zhu et al. Enterovirus D68 Sequence Variations and Pathogenicity: A Review. Viruses 2026, 18, 73

by Yi Zhu, Liting Wang and Jun Shen

Viruses 2026, 18(7), 796; https://doi.org/10.3390/v18070796 - 20 Jul 2026

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Abstract

Missing Citation [...] Full article

(This article belongs to the Section Human Virology and Viral Diseases)

23 pages, 74548 KB

Open AccessArticle

Co–Infecting Mycoviruses VdPV1 and VdMoV1 Attenuate Verticillium dahliae and Are Transmitted Vertically and Horizontally

by Yifan Wang, Guolong Gao, Jiafeng Huang, Shicheng Wang, Hongyu Ji, Yukun Liu and Yejuan Du

Viruses 2026, 18(7), 795; https://doi.org/10.3390/v18070795 - 19 Jul 2026

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Abstract

Cotton verticillium wilt caused by Verticillium dahliae severely restricts global cotton production. Mycovirus–induced hypovirulence provides a promising strategy for sustainable disease management. In this study, V. dahliae isolates from Xinjiang were screened by virome sequencing and RT–PCR, and strain 121–11C–1 co–infected with Verticillium [...] Read more.

Cotton verticillium wilt caused by Verticillium dahliae severely restricts global cotton production. Mycovirus–induced hypovirulence provides a promising strategy for sustainable disease management. In this study, V. dahliae isolates from Xinjiang were screened by virome sequencing and RT–PCR, and strain 121–11C–1 co–infected with Verticillium dahliae partitivirus 1 (VdPV1) and Verticillium dahliae magoulivirus 1 (VdMoV1) was identified. Virus–free isogenic strains were obtained via single–conidium purification, verifying that both viruses can be vertically transmitted through fungal conidia. Dual–culture assays uncovered a novel, previously unreported horizontal transmission dependency between the two viruses: VdPV1 achieves horizontal transmission only with the assistance of VdMoV1, whereas VdMoV1 can transmit independently or co–transmit with VdPV1. Biological and pathogenicity assays demonstrated that both viruses significantly inhibit mycelial growth, reduce conidial production and attenuate fungal virulence. Notably, dual infection induced a significantly stronger hypovirulent phenotype than single infection. These findings elucidate the transmission dynamics of VdPV1 and VdMoV1, expand the repertoire of hypovirulent mycoviruses in V. dahliae, and provide evidence that viral co–infection enhances fungal attenuation, offering potential applications for biological control of cotton Verticillium wilt. Full article

(This article belongs to the Collection Mycoviruses)

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15 pages, 3252 KB

Open AccessArticle

Phylogeographic Structure and Molecular Evolution of Squash Leaf Curl China Virus

by Jingwen Yu, Xue Han, Yaqin Liu, Deliang Peng, Huan Peng, Houxiang Kang, Mingjun Li, Gentu Wu, Ling Qing and Wenkun Huang

Viruses 2026, 18(7), 794; https://doi.org/10.3390/v18070794 - 19 Jul 2026

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Abstract

Squash leaf curl China virus (SLCCNV) is an important geminivirus that infects cucurbit crops and is widely distributed across Asia. To elucidate its population structure and molecular evolution, 101 DNA-A and 67 DNA-B strain sequences of SLCCNV that were publicly available from 2001 [...] Read more.

Squash leaf curl China virus (SLCCNV) is an important geminivirus that infects cucurbit crops and is widely distributed across Asia. To elucidate its population structure and molecular evolution, 101 DNA-A and 67 DNA-B strain sequences of SLCCNV that were publicly available from 2001 to 2024 were analyzed. The strains clustered into three major geographic clades, including South Asia, the Malay Archipelago, and Mainland Southeast Asia. Recombination analysis revealed breakpoints mainly concentrated in the AC2 and BC1 regions. Signals of positive selection were indicated for AC4 and AC5 by selection pressure analysis. Significant genetic differentiation among SLCCNV populations from different geographic origins, but frequent gene flow was observed between among populations from South Asia, the Malay Archipelago, and Mainland Southeast Asia. In addition, AC5 and AV2 exhibited high variability at both the nucleotide and amino acid levels, while AC1, AC2, and AC3 were relatively conserved. Collectively, the evolutionary dynamics of SLCCNV are shaped by geographic isolation, recombination events, and differential selection pressures. This study provides important insights into the molecular evolution of SLCCNV and offers valuable guidance for region-specific surveillance, quarantine strategies, and the deployment of durable resistance against emerging viral variants. Full article

(This article belongs to the Special Issue Plant Viral Pathogens: Innovations in Detection, Genetic Diversity, and Evolutionary Dynamics)

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24 pages, 10754 KB

Open AccessArticle

HSV-1 US3 Hijacks Conserved Actin Regulatory Complexes to Drive F-Actin Remodeling

by Md Imran Hossain, Md Arifuzzaman, Md Mehedi Hasan, Seung-Jong Park, Leila Rahimian, Ojasvi Dutta, Vladimir Chouljenko, Harikrishnan Mohan, Reza Ghavimi and Konstantin G. Kousoulas

Viruses 2026, 18(7), 793; https://doi.org/10.3390/v18070793 - 19 Jul 2026

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Abstract

The herpes simplex virus 1 (HSV-1) US3 is a multifunctional serine/threonine kinase that promotes HSV-1 replication and spread. But its role and the mechanisms by which US3 regulates actin cytoskeletal remodeling remain poorly defined. We combined flow cytometry, confocal microscopy, immunoprecipitation-mass spectrometry (IP-MS), [...] Read more.

The herpes simplex virus 1 (HSV-1) US3 is a multifunctional serine/threonine kinase that promotes HSV-1 replication and spread. But its role and the mechanisms by which US3 regulates actin cytoskeletal remodeling remain poorly defined. We combined flow cytometry, confocal microscopy, immunoprecipitation-mass spectrometry (IP-MS), protein complex mapping, and machine learning to characterize US3-mediated F-actin dynamics. Flow cytometry and confocal microscopy showed that wild-type HSV-1 induces significant F-actin remodeling, while the ΔUS3 mutant displays F-actin levels comparable to uninfected cells, identifying US3 as a key regulator. IP-MS identified 47 high-confidence US3 interactors enriched in conserved actin regulatory complexes, including Arp2/3 nucleation machinery, formin-associated assemblies, cofilin severing complexes, and Rho-family GTPase modules. Mapping interactors to the CORUM database revealed clustering within actin nucleation, polymerization, and severing complexes, indicating that US3 operates through organized cellular machines. Machine-learning classifiers trained on label-independent mass-spectrometry features were used to prioritize interactors resembling known actin regulators; under protein-group-aware cross-validation, logistic regression performed best (average precision 0.24; ROC-AUC 0.66), and the analysis was interpreted as prioritization rather than de novo discovery. Pharmacological inhibition of Arp2/3 and formin pathways significantly attenuated US3-dependent F-actin remodeling, supporting the functional involvement of these pathways. Together, these findings are consistent with an inferred hierarchical axis in which US3 modulates Rho GTPase signaling and cofilin activation to promote F-actin disassembly, coordinating cytoskeletal remodeling required for efficient viral egress and spread. Full article

(This article belongs to the Special Issue Unraveling Human Herpesviruses: From Molecular Mechanisms to Antiviral Approaches)

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12 pages, 2486 KB

Open AccessArticle

TRIM56 Promotes Antiviral Responses Downstream of TLR4

by Xiaohan Tong, Nan L. Li, Darong Yang, Benjamin M. Liu, Zhuoyuan Alex Li and Kui Li

Viruses 2026, 18(7), 792; https://doi.org/10.3390/v18070792 - 19 Jul 2026

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Abstract

The ubiquitin ligase protein tripartite-motif containing 56 (TRIM56) positively regulates Toll-like receptor-3 (TLR3) signaling by forming a complex with Toll-Interleukin-1 receptor domain-containing adapter protein inducing interferon (IFN)-beta (TRIF), independent of its E3 ligase activity. Whether TRIM56 modulates other TLR pathways in innate antiviral [...] Read more.

The ubiquitin ligase protein tripartite-motif containing 56 (TRIM56) positively regulates Toll-like receptor-3 (TLR3) signaling by forming a complex with Toll-Interleukin-1 receptor domain-containing adapter protein inducing interferon (IFN)-beta (TRIF), independent of its E3 ligase activity. Whether TRIM56 modulates other TLR pathways in innate antiviral immunity, however, is unclear. Herein, we show ectopic expression of TRIM56 augments activation of IFN regulatory factor-3 (IRF3)-dependent promoters following stimulation by lipopolysaccharide (LPS) in HEK293-TLR4-MD2-CD14 cells while leaving activation of NF-κB-dependent promoter unaffected, suggesting TRIM56 specifically promotes immune signaling through the TLR4-TRIF axis but not the MYD88 arm downstream of this TLR. Confirming its impact on endogenous antiviral responses in immune sentinel cells naturally harboring the TLR4 pathway, we demonstrated enforced expression of TRIM56 enhanced LPS-induced expression of IFN-beta and IFN-stimulated genes (ISGs) and establishment of an antiviral state in bone marrow-derived macrophages. Importantly, depletion of endogenous TRIM56 impaired LPS-induced antiviral gene expression and cellular antiviral defense. Altogether, these data add to understanding of the role of TRIM56 in TLR-mediated innate immune responses. Given that TRIM56 is an ISG and that many immune adjuvants and some viral proteins activate TLR4, the findings of this study could have implications for designing immunotherapies, especially those against viral infections. Full article

(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)

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21 pages, 4539 KB

Open AccessArticle

Molecular Evolution of the Chikungunya Virus E1 Gene in Saudi Arabia: Predominance of Purifying Selection and ECSA/IOL Lineage Circulation

by Mohamed A. Farrag

Viruses 2026, 18(7), 791; https://doi.org/10.3390/v18070791 - 19 Jul 2026

Viewed by 407

Abstract

Background: Chikungunya virus (CHIKV) is a re-emerging alphavirus that has caused millions of cases worldwide, yet its molecular epidemiology in Saudi Arabia remains poorly understood. This study integrates bioinformatic analysis of the envelope gene (E1) gene sequences from Saudi isolates with [...] Read more.

Background: Chikungunya virus (CHIKV) is a re-emerging alphavirus that has caused millions of cases worldwide, yet its molecular epidemiology in Saudi Arabia remains poorly understood. This study integrates bioinformatic analysis of the envelope gene (E1) gene sequences from Saudi isolates with global genotypes to characterize circulating lineages, selection pressures and stability effects of endemic mutations. Methods: A total of 109 CHIKV E1 sequences (1155 bp) representing the East/Central/South African (ECSA), Asian, and West African genotypes were retrieved from GenBank and GISAID. Phylogenetic relationships were reconstructed using maximum likelihood (IQ-TREE). Codon-based selection analyses were performed with MEME, FEL, SLAC, and FUBAR. The structural effects of nine missense mutations were assessed using DynaMut and consensus predictors (DUET, mCSM). Results: All seven Saudi isolates clustered within the ECSA-Indian Ocean Lineage (IOL) subclade with strong bootstrap support (≥95%). Short branch lengths among Saudi strains indicated recent common ancestry and limited local divergence, suggesting possible repeated introductions or limited local circulation. No codon showed robust evidence of positive selection across multiple methods. However, episodic diversifying selection was detected at codon 99 (MEME, p = 0.01), while pervasive purifying selection acted on numerous sites (e.g., codons 135, 307, 344; strong signals across FEL, SLAC, and FUBAR). A single conserved N-linked glycosylation site was present at residue 141 (NITV motif) in all Saudi and most global strains. Three mutations unique to or prominent in Saudi isolates (N20H, L136F, A249T) were identified; consensus stability predictions (DUET) classified them as destabilizing. Conclusions: Saudi CHIKV strains belong exclusively to the ECSA-IOL lineage and exhibit strong purifying selection on the E1 gene, consistent with functional constraints on this essential fusion protein. The identified Saudi-associated mutations appear to be non-adaptive, tolerated changes. These findings underscore the value of continued genomic surveillance to monitor potential adaptive evolution, particularly in the context of mass gatherings and competent Aedes vectors. Full article

(This article belongs to the Special Issue Current Trends in Arbovirus Outbreaks and Research)

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14 pages, 1777 KB

Open AccessReview

Labeling and Localization Strategies for In Situ Cryo-Electron Tomography Across the Viral Life Cycle

by Yoon Ho Park, Rana Kim, Kun-Ho Song and Hyun Suk Jung

Viruses 2026, 18(7), 790; https://doi.org/10.3390/v18070790 - 19 Jul 2026

Viewed by 510

Abstract

Cryo-electron tomography (Cryo-ET) has emerged as a transformative tool for visualizing viral components within their native cellular environment, enabling structural interrogation of viral life cycle events at nanometer resolution without chemical fixation or heavy metal staining. However, a persistent challenge in applying Cryo-ET [...] Read more.

Cryo-electron tomography (Cryo-ET) has emerged as a transformative tool for visualizing viral components within their native cellular environment, enabling structural interrogation of viral life cycle events at nanometer resolution without chemical fixation or heavy metal staining. However, a persistent challenge in applying Cryo-ET to virus research is the unambiguous identification of specific viral components within densely crowded tomographic volumes. Electron density encodes mass and shape but not molecular identity, and as the cellular environment grows more complex, the assumption that a given density has no plausible alternative assignment becomes increasingly difficult to defend. This review surveys labeling and localization strategies for in situ Cryo-ET of viral components, encompassing label-free exploitation of native electron density, Cryo-immunogold labeling, genetically encoded and synthetic molecular tags, and correlative Cryo-light/electron microscopy (Cryo-CLEM) combined with Cryo-focused ion beam (Cryo-FIB) milling. We first summarize the landmark structural discoveries that in situ Cryo-ET has delivered across virus families, and then evaluate each labeling strategy against the structural and functional constraints that viral proteins impose, providing a practical framework for matching a labeling approach to a specific viral component and life-cycle stage. Full article

(This article belongs to the Special Issue Microscopy Methods for Virus Research, 2nd Edition)

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17 pages, 6617 KB

Open AccessArticle

Composting Restructures Chicken Manure Viral Communities and Attenuates Virus-Associated Antibiotic Resistance Signals: Paired Metagenome and Virome Analyses

by Weipeng Liu, Yongfeng Wang, Jian Ma, Xiaolong Liang and Liqiong Yang

Viruses 2026, 18(7), 789; https://doi.org/10.3390/v18070789 - 19 Jul 2026

Viewed by 447

Abstract

Composting is widely used to reduce biological risks during manure recycling, but changes in viral communities and virus-associated antibiotic resistance genes (ARGs) remain poorly resolved. This study aimed to assess changes in DNA viral communities, eukaryotic viral protein signals, virus-associated ARGs, and predicted [...] Read more.

Composting is widely used to reduce biological risks during manure recycling, but changes in viral communities and virus-associated antibiotic resistance genes (ARGs) remain poorly resolved. This study aimed to assess changes in DNA viral communities, eukaryotic viral protein signals, virus-associated ARGs, and predicted virus–host linkages during chicken manure composting using paired analyses of total-community metagenomes and viral-particle-enriched viromes. Both approaches recovered viral assemblages dominated by Uroviricota and lytic viruses but produced distinct profiles. Viromes yielded more taxonomically assigned viral operational taxonomic units and a higher proportion of relatively complete viral genomes, whereas metagenomes produced a larger predicted virus–host network. Composting restructured viral communities, reducing manure-associated genera and enriching stage-specific groups. Eukaryotic viral protein signals declined during composting. Virus-associated ARGs accounted for 24.83–38.76% of ARG abundance in metagenomes and 5.38–45.09% in viromes, with lower abundance and richness in viromes. Selected virus-associated ARGs showed transient early enrichment, particularly in the virome. By maturity, both overall virus-associated ARG signals and higher-risk ARG signals had declined. Predicted virus–host associations included bacterial groups containing potential opportunistic pathogens. These results show that composting restructures viral communities and attenuates virus-associated ARG signals, while metagenomes and viromes provide complementary but non-interchangeable views of viral ecology and ARG risk. Full article

(This article belongs to the Section Bacterial Viruses)

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16 pages, 2734 KB

Open AccessArticle

Joint Monitoring and Early Warning of SARS-CoV-2 in Outdoor PM_2.5 and Wastewater

by Wenli Wang, Haizhou Liu, Dan Wang, Zhiwei Chen, Yu Jiang, Jianjun Xiang, Jing Li, Xiaoyang Zhang and Chuancheng Wu

Viruses 2026, 18(7), 788; https://doi.org/10.3390/v18070788 - 19 Jul 2026

Viewed by 360

Abstract

Background: Fine particulate matter (PM_2.5) and wastewater may carry severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and provide early signals for coronavirus disease 2019 (COVID-19) surveillance. This study investigated environmental factors affecting SARS-CoV-2 distribution in PM_2.5 and wastewater in Fuzhou. [...] Read more.

Background: Fine particulate matter (PM_2.5) and wastewater may carry severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and provide early signals for coronavirus disease 2019 (COVID-19) surveillance. This study investigated environmental factors affecting SARS-CoV-2 distribution in PM_2.5 and wastewater in Fuzhou. Methods: PM_2.5 and wastewater samples collected from January to December 2023 were tested for SARS-CoV-2 RNA using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Associations between air pollutants and meteorological factors were analyzed using generalized additive models (GAMs) and distributed lag nonlinear models (DLNMs). Results: SARS-CoV-2 was detected in 45.9% of PM_2.5 samples. PM_2.5 viral concentrations were positively associated with CO, PM_2.5, and atmospheric pressure, and negatively associated with temperature and sunshine duration. Wastewater viral concentrations were positively associated with relative humidity and precipitation and negatively associated with NO₂ and SO₂. PM_2.5 signals showed the strongest lag effect at approximately 2 days, while wastewater signals peaked at lag 0. The lag effect herein describes the time interval between environmental SARS-CoV-2 signals and predicted COVID-19 outpatient cases. Elderly populations showed higher environmental sensitivity, with sex-specific differences observed. Conclusions: SARS-CoV-2 signals in PM_2.5 and wastewater reflected COVID-19 trends. Integrated multi-media monitoring may improve early warning and support targeted public health interventions. Full article

(This article belongs to the Section Human Virology and Viral Diseases)

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12 pages, 15302 KB

Open AccessReview

Structural Basis of Intermolecular Interactions Between APOBEC3 and HIV-1 Vif

by Hirotaka Ode and Yasumasa Iwatani

Viruses 2026, 18(7), 787; https://doi.org/10.3390/v18070787 - 19 Jul 2026

Viewed by 459

Abstract

The human APOBEC3 (A3) family of cytidine deaminases, including A3G, A3F, and A3H, participates in cellular anti-retroviral immunity. In contrast, to antagonize the anti-retroviral activities of these A3 family proteins, HIV-1 produces its gene product called viral infectivity factor (Vif) in infected cells. [...] Read more.

The human APOBEC3 (A3) family of cytidine deaminases, including A3G, A3F, and A3H, participates in cellular anti-retroviral immunity. In contrast, to antagonize the anti-retroviral activities of these A3 family proteins, HIV-1 produces its gene product called viral infectivity factor (Vif) in infected cells. Vif is a pleiotropic hub protein that specifically binds to various A3 proteins with the aid of host core-binding factor subunit β (CBF-β) and mediates their proteasomal degradation. To date, numerous biological and structural studies have been performed to understand the arms race between A3 and Vif. Previous extensive mutagenesis and structural analyses have suggested that there are three distinct types of Vif-binding interfaces among human A3s and three largely nonoverlapping interfaces on Vif for binding with these A3s. Moreover, recent cryo-electron microscopy (cryo-EM) structural analyses have clarified further details of the different intermolecular interactions of Vif with each of three human A3s (A3G, A3F, and A3H) and have proposed a possible mechanism by which one Vif molecule can recognize all three types of A3s. In this review, we summarize the current understanding of the structural basis of the interaction between A3 and Vif. This information may be helpful for developing drugs targeting these interfaces. Full article

(This article belongs to the Special Issue Intrinsic Immunity vs. Viral Antagonism: Which One Bites the Dust?)

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19 pages, 4443 KB

Open AccessArticle

Development and Preliminary Field Evaluation of an Indirect ELISA for Detecting Tomato Yellow Leaf Curl Virus

by Zeling Zhang, Yifan Liu, Xiangyu Zhang, Xianle Xue and Ting Xu

Viruses 2026, 18(7), 786; https://doi.org/10.3390/v18070786 - 19 Jul 2026

Viewed by 312

Abstract

Tomato yellow leaf curl virus (TYLCV) is a major threat to tomato production, creating a need for sensitive, low-cost detection methods that can be applied to early symptomatic or low-viral-load samples. Recombinant antigen configuration may influence serological assay development, although the specific contribution [...] Read more.

Tomato yellow leaf curl virus (TYLCV) is a major threat to tomato production, creating a need for sensitive, low-cost detection methods that can be applied to early symptomatic or low-viral-load samples. Recombinant antigen configuration may influence serological assay development, although the specific contribution of multiple-cloning-site (MCS)-derived intermediate sequences remains uncertain. In this study, a recombinant Trx-His-coat protein (CP) fusion antigen was produced using an MCS-free direct-fusion construct that retained the Trx-His tag while removing the MCS-derived intermediate sequence, followed by gradient refolding. No direct comparison with linker-containing, tag-cleaved, or tag-free antigen constructs was performed. The purified antigen was used to immunize rabbits and generate a high-titre polyclonal antibody (pAb). The resulting indirect enzyme-linked immunosorbent assay (ELISA) achieved a theoretical limit of detection of 1.8 ng/mL and an estimated pre-dilution equivalent the limit of detection (LOD) of 72 ng/mL after sample dilution. The assay showed favourable tolerance to crude tomato leaf matrices, with spike-recovery rates of 95.45–100.40%. In a preliminary evaluation using a balanced panel of 32 field-collected samples, ELISA absorbance correlated with droplet digital PCR quantification (R² = 0.9819) and plant disease index values (R² = 0.9774). Liquid chromatography–tandem mass spectrometry (LC-MS/MS) peptide mapping and AlphaFold2-based modelling were used only to provide preliminary computational context for antigen interpretation. The assay showed cross-recognition toward Tobacco curly shoot virus (TbCSV), indicating that it should not be considered strictly TYLCV species-specific. Therefore, this assay may support preliminary serological screening under the tested conditions, whereas molecular confirmation remains necessary when species-level identification is required. Full article

(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)

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11 pages, 252 KB

Open AccessArticle

Increasing Frequency of Secondary Dengue Infections in Sequential Outbreaks (2016–2024)—Clinical Impact and Diagnostic Challenges

by Sonia L. Espindola, Matías Javier Pereson, José Martín Lema, Analía Kachuk, Graciela M. Carballo, Natalia Aloisi, María Noel Badano, Marcos Miretti, Federico A. Di Lello and Patricia Baré

Viruses 2026, 18(7), 785; https://doi.org/10.3390/v18070785 - 18 Jul 2026

Viewed by 401

Abstract

Successive dengue virus (DENV) outbreaks progressively reshape population immunity, influencing disease expression and diagnostic performance. This study evaluated the impact of secondary infections across sequential outbreaks on disease severity markers, serotype dynamics, and the agreement between routinely used direct diagnostic methods. This retrospective [...] Read more.

Successive dengue virus (DENV) outbreaks progressively reshape population immunity, influencing disease expression and diagnostic performance. This study evaluated the impact of secondary infections across sequential outbreaks on disease severity markers, serotype dynamics, and the agreement between routinely used direct diagnostic methods. This retrospective study analyzed 976 serum samples from three outbreaks in Misiones, Argentina. Clinical and serotype analyses included 869 acute-phase dengue cases confirmed by at least one direct detection method (2016: n = 512; 2019: n = 148; 2024: n = 209). A subset of 318 samples, including 107 RT-PCR/NS1-negative samples, was used to compare NS1 antigen rapid diagnostic tests (NS1 Ag) and RT-PCR. Viral serotypes and clinical and laboratory severity markers were evaluated. Secondary infections increased from 31.1% in 2016 to 43.2% in 2019 and 53.1% in 2024 (p < 0.001). Serotype distribution shifted from DENV-1 predominance in 2016 (95.1%) to DENV-1/DENV-4 co-circulation in 2019 (60.7%/39.3%) and DENV-2 predominance in 2024 (97.6%). Secondary infections were associated with increased frequency of laboratory severity markers, particularly in 2024, including higher hematocrit, liver enzyme levels and lower leukocyte and platelet counts. Concordance between NS1 Ag and RT-PCR was lower in secondary infections (κ = 0.457 vs. 0.759, p = 0.0013). The increasing frequency of secondary infections may influence laboratory markers associated with dengue severity and reduce the diagnostic concordance between direct detection methods, highlighting the need for optimized surveillance and diagnostic strategies during dengue outbreaks. Full article

(This article belongs to the Special Issue Current Trends in Arbovirus Outbreaks and Research)

12 pages, 1403 KB

Open AccessArticle

Epidemiological Trends, Transmission Dynamics, and Mortality Patterns of HIV/AIDS in South Korea, 1985–2024: A Comprehensive Regression and Time Series Analysis with Projections to 2028

by Hyeran Jung and Minsun Jung

Viruses 2026, 18(7), 784; https://doi.org/10.3390/v18070784 - 17 Jul 2026

Viewed by 343

Abstract

Background: South Korea has documented HIV cases since 1985; however, comprehensive longitudinal analyses integrating incidence, mortality, transmission dynamics, and immunological staging across the full surveillance period remain limited. This study aimed to characterize epidemiological trends from 1985 to 2024 and project future trajectories [...] Read more.

Background: South Korea has documented HIV cases since 1985; however, comprehensive longitudinal analyses integrating incidence, mortality, transmission dynamics, and immunological staging across the full surveillance period remain limited. This study aimed to characterize epidemiological trends from 1985 to 2024 and project future trajectories through 2028. Methods: We analyzed nationally reported aggregate HIV/AIDS surveillance data from the Korea Disease Control and Prevention Agency (KDCA) via KOSIS (1985–2024). Annual HIV incidence, AIDS case notifications, HIV-related mortality, transmission route distributions, CD4+ T-cell counts at diagnosis, and cumulative prevalent cases stratified by sex were examined. Statistical methods included simple and multiple linear regression, Pearson and Spearman correlation, hierarchical regression analysis, and time series forecasting using Holt–Winters exponential smoothing and ARIMA (AutoRegressive Integrated Moving Average) modeling. Missing data in transmission route classification (29.6% non-response in 2024) were addressed through sensitivity analysis and explicit discussion of potential misclassification bias. Results: HIV annual incidence increased significantly from one case in 1985 to a peak of 1081 in 2014 (slope = +39.25 cases/year, R² = 0.912, p < 0.001), followed by a significant decline to 714 cases in 2024 (slope = −38.76 cases/year, R² = 0.879, p < 0.001). A strong positive correlation was observed between HIV and AIDS incidence (Pearson r = 0.627, p = 0.017; Spearman ρ = 0.785, p < 0.001). The AIDS/HIV notification ratio declined significantly from 0.307 in 2011 to 0.196 in 2024 (slope = −0.006/year, R² = 0.421, p = 0.012). The male-to-female notification ratio increased from 0.8:1 in 1987 to 22.0:1 in 2024 (R² = 0.600, p < 0.001). Among reported sexual transmissions, the proportion attributable to MSM increased from 0% in 1985 to 63.7% in 2024 (slope = +1.30%/year, R² = 0.804, p < 0.001). The proportional mortality rate declined significantly from 2.31% in 2011 to 0.93% in 2024 (slope = −0.105%/year, R² = 0.821, p < 0.001). Time series forecasting projected continued decline to approximately 666 new HIV cases and 105 AIDS notifications annually by 2028. Conclusions: The South Korean HIV epidemic has undergone a profound epidemiological transition—from heterosexual-predominant early growth through a 2014 peak toward a declining, MSM-concentrated trajectory—with mortality progressively decoupled from incidence through expanded antiretroviral therapy coverage. Targeted MSM-focused prevention, expansion of PrEP access, and sustained ART scale-up are essential to achieving national HIV elimination targets. Full article

(This article belongs to the Special Issue Epidemiology and Prevention of HIV/AIDS)

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26 pages, 7054 KB

Open AccessArticle

Neuroinflammation, Pericyte Dysfunction, and Alzheimer’s Disease-Associated Gene Expression and Pathway Activation in the Brain of SARS-CoV-2-Infected Mice

by Akinkunmi O. Lawal, Ikechukwu B. Jacob, Vignesh Karnik, Hongkuan Fan, Saravanan Thangamani, Paul T. Massa and Guirong Wang

Viruses 2026, 18(7), 783; https://doi.org/10.3390/v18070783 - 17 Jul 2026

Viewed by 1729

Abstract

SARS-CoV-2 infection leads to extrapulmonary complications in multiple organs, including the brain, both in the short-term and long-term. The neurological manifestation of SARS-CoV-2 infection ranges from benign signs like loss of smell and loss of taste to severe complications like encephalitis, stroke, and [...] Read more.

SARS-CoV-2 infection leads to extrapulmonary complications in multiple organs, including the brain, both in the short-term and long-term. The neurological manifestation of SARS-CoV-2 infection ranges from benign signs like loss of smell and loss of taste to severe complications like encephalitis, stroke, and exacerbation of Alzheimer’s disease (AD) progression. Pericytes are mural cells of the brain vasculature that help maintain the blood–brain barrier (BBB), regulate cerebral blood flow (CBF), modulate neuroinflammation, and clear toxic materials, including amyloid beta. Pericytes express ACE2, the receptor for SARS-CoV-2, and therefore may be targeted by either direct virus infection or virus-induced inflammatory cytokines induced by the virus in the brain. To further study the effects of SARS-CoV-2 on pericytes and BBB integrity, the long-term effects of SARS-CoV-2 infection on brain pericytes, inflammation, and other neuropathological complications were analyzed in mice. K18 (human ACE2 transgenic) mice were infected with 10³ PFU of SARS-CoV-2 (delta strain), and the brains were analyzed at 6, 14, and 30 days post-infection (dpi). A significant reduction in the weight of infected mice was observed by 6 dpi. Viral nucleocapsid protein and infectious SARS-CoV-2 were observed in the brains of all mice by 6 dpi, and in some mice by 14 dpi, but not at 30 dpi. This observation suggests viral neurotropism with subsequent clearance at later timepoints. Despite virus clearance, the levels of inflammatory mediators, including TNF-α and IFN-γ were significantly elevated up to 30 dpi. We also observed a significant reduction in the level of brain pericytes by 14 dpi up to 30 dpi. Importantly, an increase was observed in the level of Friend Leukemia Integration 1 (FLI-1), a transcription factor known to promote pericyte cell death, from 14 dpi up to 30 dpi. The level of amyloid beta 1–42 was elevated in the brain of infected mice at 6 dpi, and this was maintained up to 30 dpi, and there was a decrease in neuronal density from 14 to 30 dpi. Furthermore, we observed an increased expression of Alzheimer’s disease (AD)-associated genes like PSEN1, BACE1, and APP. Furthermore, there was increased activation of several neurodegenerative pathways, including “G alpha (z) signaling pathway”, “Apelin muscle signaling pathway”, and “G beta-gamma (Gβγ) signaling”, in the brains of infected mice compared to control mice. Collectively, the observed neuropathology and unique molecular markers of neurodegenerative disease progression provide a novel mechanism by which COVID-19 may promote dementia/AD by contributing to pericyte loss and BBB dysfunction during infection. Full article

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9 pages, 262 KB

Open AccessCommentary

Exploring the Potential Contribution of Climate-Informed Research to Future Ebola Preparedness in Central Africa

by Sandra Ndaka Sumbu and Ben Bepouka

Viruses 2026, 18(7), 782; https://doi.org/10.3390/v18070782 - 16 Jul 2026

Viewed by 491

Abstract

The ongoing 2026 Bundibugyo ebolavirus outbreak in eastern Democratic Republic of the Congo highlights the continued vulnerability of Central Africa to recurrent Ebola emergence. This outbreak emerged less than six months after the previous one ended, appears to represent one of the shortest [...] Read more.

The ongoing 2026 Bundibugyo ebolavirus outbreak in eastern Democratic Republic of the Congo highlights the continued vulnerability of Central Africa to recurrent Ebola emergence. This outbreak emerged less than six months after the previous one ended, appears to represent one of the shortest documented inter-epidemic intervals in the Democratic Republic of the Congo based on currently available outbreak reports. Current surveillance systems remain largely reactive, focusing on the detection of human cases after zoonotic spillover has occurred. While strengthening health systems, diagnostic capacity, and early case detection remains the cornerstone of Ebola preparedness, growing research suggests that environmental and climatic information may eventually contribute to a broader understanding of spillover risk within a One Health framework. However, current evidence remains insufficient to identify validated environmental indicators or operational thresholds capable of predicting Ebola spillover events. Recent modeling studies have demonstrated that environmental drivers of Ebola emergence remain highly context-dependent and cannot yet support operational early warning systems. This commentary argues that continued research integrating environmental monitoring, remote sensing, ecological observations, and epidemiological data may improve understanding of Ebola emergence and eventually contribute to future preparedness strategies. Rather than proposing climate-informed preparedness approaches as an operational prediction tool, we emphasize its potential as a complementary research priority requiring further validation before any operational implementation. Full article

(This article belongs to the Special Issue The 2026 Central Africa (Bundibugyo) Ebola Virus Outbreak—and Lessons Learned from Previous Ebola Virus Episodes)

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34 pages, 2474 KB

Open AccessReview

Avian Metapneumovirus: Current Knowledge, Critical Gaps, and Future Directions in Transmission, Pathogenesis, and Control Across Poultry Systems

by Abhijith Anil, Biswash Ghimire, Menuka Bhandari and Kush Kumar Yadav

Viruses 2026, 18(7), 781; https://doi.org/10.3390/v18070781 - 16 Jul 2026

Viewed by 868

Abstract

Avian metapneumovirus (aMPV) is an economically significant respiratory virus of poultry that causes major losses due to reduced egg production and increased susceptibility to secondary infections. It has global significance in poultry production systems and mainly affects turkeys, chickens, and ducks. It was [...] Read more.

Avian metapneumovirus (aMPV) is an economically significant respiratory virus of poultry that causes major losses due to reduced egg production and increased susceptibility to secondary infections. It has global significance in poultry production systems and mainly affects turkeys, chickens, and ducks. It was first detected in South Africa in 1978 and is classified into four distinct subtypes (A–D) based upon sequence divergence of the glycoprotein (G) gene. Subtype C has historically been the dominant subtype in the US, first detected in the late 1990s, causing approximately $15 million economic loss per year in Minnesota alone. However, after a decade, aMPV re-emerged in the fall of 2023. Subtype A in California and B in North Carolina was detected for the very first time in the US, impacting multiple states, with an estimated $112 million loss in Minnesota alone. The most recent US Animal Health Association (USAHA) annual survey has now ranked aMPV as the most frequently reported issue in turkey production. Even after four decades of virus identification, areas such as transmission routes, host–virus interactions and tissue tropism within the host are not studied in detail. Addressing these gaps via current modernized research tools is crucial in minimizing the impact of aMPV on the poultry industry. Therefore, this review article summarizes current knowledge on aMPV while identifying critical research gaps and emphasizing future research directions for combating aMPV and supporting long-term sustainability of the turkey industry. Full article

(This article belongs to the Special Issue Viral Surveillance, Transmission, Pathogenesis, and Vaccine Development in Domestic Animals and Wildlife)

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13 pages, 1003 KB

Open AccessReview

Age-Dependent Differences in the Antiviral Response of the Respiratory Epithelium

by Leah Setar and Bria Coates

Viruses 2026, 18(7), 780; https://doi.org/10.3390/v18070780 - 16 Jul 2026

Viewed by 552

Abstract

Age is an established risk factor for severe viral respiratory infections, yet the mechanisms driving increased severity of illness in infants and older adults remain incompletely understood. The respiratory epithelium is the primary target of viral infection and how it orchestrates the immune [...] Read more.

Age is an established risk factor for severe viral respiratory infections, yet the mechanisms driving increased severity of illness in infants and older adults remain incompletely understood. The respiratory epithelium is the primary target of viral infection and how it orchestrates the immune response may be a key determinant of clinical outcomes. The profound age-related difference in susceptibility to severe Coronavirus disease 2019 (COVID-19) brought increased attention to the epithelial response to viral infection in children and adults, adding significant data to the preexisting body of work largely focused on influenza and respiratory syncytial virus (RSV). This review synthesizes current knowledge on the structural and functional differences in the respiratory epithelium between children and adults at baseline and during viral infection. We review the variable and heterogenous human studies in addition to in vitro and animal model data to identify key gaps in current knowledge. Here, we advocate for a more complete understanding of age-dependent differences in the respiratory epithelial response to viral infection to uncover therapeutic targets for prevention and treatment of viral-associated respiratory failure. Full article

(This article belongs to the Special Issue Advances in Understanding Viral Pathogenesis and Host Immune Responses to Arboviruses and Respiratory Viruses)

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22 pages, 4932 KB

Open AccessArticle

Competitive Fitness of Cytomegalovirus Mutants Bearing Changes in the UL56 Terminase Subunit, Associated with Letermovir-Resistance, in Presence and Absence of Antivirals

by Graciela Andrei, Sarah Gillemot and Robert Snoeck

Viruses 2026, 18(7), 779; https://doi.org/10.3390/v18070779 - 15 Jul 2026

Viewed by 488

Abstract

Letermovir (LMV), a cytomegalovirus (CMV) terminase inhibitor, has a potentially low genetic barrier to the emergence of resistance, with single mutations in the terminase subunits (UL51, UL56, UL89) being associated with LMV resistance (LMV-R). We determined the fitness of LMV-R viruses (UL56 C325F/W/Y [...] Read more.

Letermovir (LMV), a cytomegalovirus (CMV) terminase inhibitor, has a potentially low genetic barrier to the emergence of resistance, with single mutations in the terminase subunits (UL51, UL56, UL89) being associated with LMV resistance (LMV-R). We determined the fitness of LMV-R viruses (UL56 C325F/W/Y or M236V mutants) with different DNA polymerase (pol) (UL54) mutants in the presence and absence of anti-CMV drugs in dual-infection competition assays. After 7 days of growth, viral variants were quantified by targeted sequencing of the UL54 or UL56 genes by next-generation sequencing. Without antivirals, the UL56 C325F mutant was equally fitted as the wild-type virus, in contrast to C325W/Y mutants that had a reduced replication capacity. The UL56 C325F mutant showed the highest replication capacity among all terminase mutants tested when grown in competition with wild-type virus under LMV. The UL56 terminase mutants gained replication capacity when grown in competition with DNA pol mutant viruses under LMV pressure, with the terminase mutant UL56 C325F being able to overgrow various DNA pol mutants. Furthermore, the UL56 C325F mutant showed the highest replication capacity when grown in competition with another UL56 terminase mutant. Our results are in line with the C325F UL56 mutant being the most frequent LMV-R mutation identified in the clinic. Full article

(This article belongs to the Section Human Virology and Viral Diseases)

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14 pages, 765 KB

Open AccessArticle

Biomarkers and Risk Factors Associated with Apnea in Hospitalized Infants with Acute Respiratory Infection

by Julia Dvorkin, Maria Pico, Josefina L. Razzini, Romina Libster, Fernando P. Polack, Mauricio T. Caballero and on behalf of The INFANT Respiratory Network

Viruses 2026, 18(7), 778; https://doi.org/10.3390/v18070778 - 15 Jul 2026

Viewed by 457

Abstract

Apnea is a potentially life-threatening complication of severe acute respiratory infection (SARI) in early infancy; however, its determinants remain incompletely understood. Between 2011 and 2013, we conducted a population-based, cross-sectional, multicenter study in Buenos Aires, Argentina. We examined epidemiological, clinical, virological, and immunological [...] Read more.

Apnea is a potentially life-threatening complication of severe acute respiratory infection (SARI) in early infancy; however, its determinants remain incompletely understood. Between 2011 and 2013, we conducted a population-based, cross-sectional, multicenter study in Buenos Aires, Argentina. We examined epidemiological, clinical, virological, and immunological factors associated with apnea in a population-based cohort of 2376 infants younger than five months hospitalized due to SARI. Using hierarchical multivariable logistic regression, we identified preterm birth, cesarean section, previous NICU admission, age under two months, and severe household crowding as independent predictors of apnea. RSV infection was inversely associated with apnea, and IL-5 levels in respiratory secretions were significantly lower among infants with apnea, suggesting a qualitatively different immune response in this group. Taken together, these findings indicate that apnea during SARI in early infancy is primarily driven by biological immaturity and adverse environmental conditions. Full article

(This article belongs to the Special Issue Advances in Understanding Viral Pathogenesis and Host Immune Responses to Arboviruses and Respiratory Viruses)

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17 pages, 963 KB

Open AccessReview

Regulatory Implications and Control Measures for Lumpy Skin Disease, Highly Pathogenic Avian Influenza, and Foot-and-Mouth Disease in European Livestock

by Carolina Baptista, Bart de Leeuw, Valentina Busin, Jobke Van Hout-van Dijk, Max Bastian, Rachael Tarlinton, Nancy De Briyne and Wiebke Jansen

Viruses 2026, 18(7), 777; https://doi.org/10.3390/v18070777 - 15 Jul 2026

Viewed by 599

Abstract

(1) Background: Transboundary notifiable infectious viral diseases, such as lumpy skin disease (LSD), highly pathogenic avian influenza (HPAI), and foot-and-mouth disease (FMD), continue to severely disrupt Europe’s animal health and welfare, food security, and the multi-burdened livestock sector. (2) Methods: Through an extensive [...] Read more.

(1) Background: Transboundary notifiable infectious viral diseases, such as lumpy skin disease (LSD), highly pathogenic avian influenza (HPAI), and foot-and-mouth disease (FMD), continue to severely disrupt Europe’s animal health and welfare, food security, and the multi-burdened livestock sector. (2) Methods: Through an extensive literature search, with data collected from the scientific literature, outbreak notifications, and European Union (EU) policy reports, this study synthesises evidence on the economic and societal impacts of preventive mass vaccination compared with stamping out for listed viral animal diseases in Europe. (3) Results: Evidence from LSD, HPAI, and FMD indicates that preventive vaccination reduces outbreak size, duration, and associated economic losses, particularly in high-risk and endemic settings. For LSD, vaccination is essential in eradication, as culling alone fails. For HPAI, evolving epidemiology supports vaccination-to-live strategies. In contrast, for FMD, despite epidemiological benefits of vaccination, the maintenance of FMD-free status without vaccination remains the dominant policy objective, constraining adoption of vaccination-to-live due to trade implications. (4) Conclusions: Overall, findings support the following recommendations: shifting toward preventive vaccination tailored by country and disease, prioritising vaccine-to-live strategies within a harmonised regulatory framework, and strengthening differentiating infected from vaccinated animals (DIVA)-based surveillance and trade-compatible frameworks, all sensible approaches to protect animal welfare and economic stability in Europe’s livestock sector. Full article

(This article belongs to the Special Issue New Findings in Animal Biosecurity Related to Viral Diseases)

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Viruses, Volume 18, Issue 7 (July 2026) – 116 articles

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