Viruses

32 pages, 1658 KiB

Open AccessReview

Advances in Viroporin Function and Structure: A Comparative Analysis of Alphavirus 6K with Well-Characterized Viroporins

by Vashi Negi, Andrew S. Miller and Richard J. Kuhn

Viruses 2025, 17(6), 868; https://doi.org/10.3390/v17060868 - 19 Jun 2025

Abstract

Viruses encode ion channel proteins called viroporins to assist in infection and immune evasion. The alphavirus 6K protein is classified as a member of the viroporin family of proteins. Several studies have characterized the role of 6K in alphavirus budding and infection since [...] Read more.

Viruses encode ion channel proteins called viroporins to assist in infection and immune evasion. The alphavirus 6K protein is classified as a member of the viroporin family of proteins. Several studies have characterized the role of 6K in alphavirus budding and infection since its discovery in the late 1970s. In this review, we summarize 6K research and discuss some unanswered questions regarding 6K biology. We highlight the similarities and differences between 6K and viroporins of clinically relevant viruses—influenza A virus, HIV-1, hepatitis C virus, and SARS-CoV-2—and address their importance as therapeutic targets. The sensitivity of these viroporins to common inhibitors and their ability to functionally complement each other underscore their potential as targets for broad-spectrum antiviral therapies. Full article

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

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9 pages, 1223 KiB

Open AccessBrief Report

Discovery of a Novel Parahenipavirus, Parahenipavirus_GH, in Shrews in South Korea, 2022

by Gyuri Sim, Chi-Hwan Choi, Minji Lee, Hak Seon Lee, Seong Yoon Kim, Seung Hun Lee, Hee Il Lee and Yoon-Seok Chung

Viruses 2025, 17(6), 867; https://doi.org/10.3390/v17060867 - 19 Jun 2025

Abstract

Highly pathogenic henipaviruses (Nipah and Hendra viruses) and parahenipaviruses (Langya virus) have demonstrated significant zoonotic potential. We aimed to identify Henipavirus or Parahenipavirus species in rodents and shrews in South Korea to underline the potential zoonotic transmission risk. Kidney and lung tissues from [...] Read more.

Highly pathogenic henipaviruses (Nipah and Hendra viruses) and parahenipaviruses (Langya virus) have demonstrated significant zoonotic potential. We aimed to identify Henipavirus or Parahenipavirus species in rodents and shrews in South Korea to underline the potential zoonotic transmission risk. Kidney and lung tissues from 285 rodents and shrews were screened for Henipavirus and Parahenipavirus using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) targeting the Gamak virus and Daeryong virus (DARV) sequences. Based on the qRT-PCR results, 75 out of the 285 individuals tested positive, with the highest viral loads in the kidneys of Apodemus agrarius, Crocidura lasiura, and Crocidura shantungensis. A kidney sample from C. shantungensis that exhibited the lowest Ct value was further analyzed using PCR, Sanger sequencing, and metagenomic analysis, yielding a near-complete genome of a novel Parahenipavirus, designated Parahenipavirus_GH (PHNV-GH), which is phylogenetically related to DARV and Jingmen virus but exhibits distinct genomic features. Ixodes granulatus ticks were also identified on the host shrew. The identification of PHNV-GH in southern South Korea expands the known geographical distribution range of parahenipaviruses and highlights the ongoing risk of zoonotic transmission. Given the uncertain transmission dynamics and pathogenic potential of parahenipaviruses, comprehensive environmental surveillance and characterization of emerging parahenipaviruses are essential for preventing future outbreaks. Full article

(This article belongs to the Special Issue Emerging Zoonotic Paramyxoviruses)

17 pages, 5218 KiB

Open AccessReview

Trafficking and Activation of Henipavirus, Parahenipavirus, and Henipa-like Virus Fusion Proteins

by Chanakha K. Navaratnarajah and Roberto Cattaneo

Viruses 2025, 17(6), 866; https://doi.org/10.3390/v17060866 - 19 Jun 2025

Abstract

Henipaviruses are emerging zoonotic viruses that have caused deadly outbreaks in humans and livestock across several regions of the world. The fusion (F) protein of henipaviruses plays a critical role in viral entry into host cells and represents a key determinant of viral [...] Read more.

Henipaviruses are emerging zoonotic viruses that have caused deadly outbreaks in humans and livestock across several regions of the world. The fusion (F) protein of henipaviruses plays a critical role in viral entry into host cells and represents a key determinant of viral pathogenicity. This review provides a comprehensive analysis of current knowledge regarding trafficking, activation, as well as the role in particle assembly, of henipavirus F proteins. We discuss the unique characteristics of henipavirus F proteins compared to other paramyxovirus fusion proteins, with particular emphasis on their distinctive trafficking and activation mechanisms. Attention is also given to novel henipaviruses that have been detected in hosts other than bats, namely rodents and shrews. These viruses are sufficiently different that the International Committee on Taxonomy of Viruses has proposed a new genus for them, the Parahenipaviruses. We discuss how variations in F protein characteristics between Henipaviruses, Parahenipaviruses, and yet-unclassified henipa-like viruses might influence their trafficking and activation. Understanding these molecular mechanisms is crucial for developing effective therapeutic strategies against henipavirus infections and for predicting the emergence of novel henipavirus strains with pandemic potential. Full article

(This article belongs to the Special Issue 15-Year Anniversary of Viruses)

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17 pages, 1812 KiB

Open AccessReview

The Multigene Family Genes-Encoded Proteins of African Swine Fever Virus: Roles in Evolution, Cell Tropism, Immune Evasion, and Pathogenesis

by Ruojia Huang, Rui Luo, Jing Lan, Zhanhao Lu, Hua-Ji Qiu, Tao Wang and Yuan Sun

Viruses 2025, 17(6), 865; https://doi.org/10.3390/v17060865 - 19 Jun 2025

Abstract

African swine fever virus (ASFV), the causative agent of African swine fever (ASF), poses a catastrophic threat to global swine industries through its capacity for immune subversion and rapid evolution. Multigene family genes (MGFs)-encoded proteins serve as molecular hubs governing viral evolution, immune [...] Read more.

African swine fever virus (ASFV), the causative agent of African swine fever (ASF), poses a catastrophic threat to global swine industries through its capacity for immune subversion and rapid evolution. Multigene family genes (MGFs)-encoded proteins serve as molecular hubs governing viral evolution, immune evasion, cell tropism, and disease pathogenesis. This review synthesizes structural and functional evidence demonstrating that MGFs-encoded proteins suppress both interferon signaling and inflammasome activation, while their genomic plasticity in variable terminal regions drives strain diversification and adaptation. Translationally, targeted deletion of immunomodulatory MGFs enables the rational design of live attenuated vaccines that improve protective efficacy while minimizing residual virulence. Moreover, hypervariable MGFs provide strain-specific signatures for PCR-based diagnostics and phylogeographic tracking, directly addressing outbreak surveillance challenges. By unifying virology with translational innovation, this review establishes MGFs as priority targets for next-generation ASF countermeasures. Full article

(This article belongs to the Collection African Swine Fever Virus (ASFV))

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6 pages, 180 KiB

Open AccessCase Report

Brainstem Encephalitis: An Atypical Manifestation of Zika Virus Infection in Brazil

by Mateus Santana do Rosário, Pedro Antonio Pereira de Jesus, Italo Andrade Barbosa Lima, Marcos Vinicius Oliveira Francisco, Cleiton Silva Santos, Lorena Cunha Martins, Luiza Vieira Luedy Trindade, Ricardo Khouri and Isadora Cristina de Siqueira

Viruses 2025, 17(6), 864; https://doi.org/10.3390/v17060864 - 18 Jun 2025

Abstract

Zika virus (ZIKV), once considered a relatively benign pathogen, has emerged as a cause of severe neurological complications, including Guillain-Barrè Syndrome and encephalitis. This report presents the case of a 21-year-old Brazilian woman who initially presented with fever, rash, and arthralgia. Seven days [...] Read more.

Zika virus (ZIKV), once considered a relatively benign pathogen, has emerged as a cause of severe neurological complications, including Guillain-Barrè Syndrome and encephalitis. This report presents the case of a 21-year-old Brazilian woman who initially presented with fever, rash, and arthralgia. Seven days later, she developed confusion, speech impairment, and gait disturbance. Following a tonic-clonic seizure, neurological examination revealed dysphonia, dysarthria and facial palsy, suggestive of brainstem involvement. ZIKV infection was detected by positive IgM serology and a plaque reduction neutralization test. The patient was treated with corticosteroids and antiepileptic drugs, leading to substantial clinical improvement, and discharge after 25 days of hospitalization. This case underscores the neuroinvasive potential of ZIKV and highlights the importance of early recognition and management of atypical neurological manifestations. It also reinforces the need to consider ZIKV in the differential diagnosis of encephalitis, particularly in endemic regions, and contributes to the growing understanding of ZIKV neurotropism and possible therapeutic approaches for severe presentations. Full article

(This article belongs to the Special Issue Mosquito-Borne Encephalitis Viruses)

10 pages, 1350 KiB

Open AccessBrief Report

Complete Genome and Recombination Analysis of a Novel Porcine Reproductive and Respiratory Syndrome Virus 2 (Variant 1H.18) Identified in the Midwestern USA

by Joao P. Herrera da Silva, Stephanie Rossow, Igor A. D. Paploski, Mariana Kikuti, Cesar A. Corzo and Kimberly VanderWaal

Viruses 2025, 17(6), 863; https://doi.org/10.3390/v17060863 - 18 Jun 2025

Abstract

Porcine Reproductive and Respiratory Syndrome Virus 2 (PRRSV-2) represents one of the greatest threats to global pork production. Increased incidence of a genetic variant of Porcine Reproductive and Respiratory Syndrome Virus (variant 1H.18) was recently reported in the Midwestern USA Sequence comparisons in [...] Read more.

Porcine Reproductive and Respiratory Syndrome Virus 2 (PRRSV-2) represents one of the greatest threats to global pork production. Increased incidence of a genetic variant of Porcine Reproductive and Respiratory Syndrome Virus (variant 1H.18) was recently reported in the Midwestern USA Sequence comparisons in the ORF5 region indicate that 1H.18 was closely related to both sub-lineages L1H and L1C. To expand our understanding and attempt to elucidate the origin of the 1H.18, we sequenced a near-complete genome, covering all coding regions, and investigated the occurrence of recombination events that may have contributed to the emergence of the new variant. At least six distinct recombination events were identified across the coding portion of the genome. Evidence of recombination in the ORF5 region between variants 1H.31 and 1C.3 was detected. Our results suggest a likely origin of 1H.18 driven by recombination. Full article

(This article belongs to the Special Issue Research Progress on Porcine Reproductive and Respiratory Syndrome Virus)

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10 pages, 576 KiB

Open AccessBrief Report

First Molecular Evidence of Equine Herpesvirus Type 1 (EHV-1) in Ocular Swabs of Clinically Affected Horses

by Beatriz Musoles-Cuenca, Miguel Padilla-Blanco, Valentina Vitale, Teresa Lorenzo-Bermejo, María de la Cuesta-Torrado, Beatriz Ballester, Elisa Maiques, Consuelo Rubio-Guerri and Ana Velloso Alvarez

Viruses 2025, 17(6), 862; https://doi.org/10.3390/v17060862 - 18 Jun 2025

Abstract

Equine Herpesvirus Type 1 (EHV-1) is a significant pathogen within the Alphaherpesvirinae subfamily, causing respiratory disease, abortions, and, in severe cases, equine herpesvirus myeloencephalopathy (EHM). While nasal swabs and blood samples are commonly used for real-time polymerase chain reaction (RT-PCR) diagnosis, variability in [...] Read more.

Equine Herpesvirus Type 1 (EHV-1) is a significant pathogen within the Alphaherpesvirinae subfamily, causing respiratory disease, abortions, and, in severe cases, equine herpesvirus myeloencephalopathy (EHM). While nasal swabs and blood samples are commonly used for real-time polymerase chain reaction (RT-PCR) diagnosis, variability in viral shedding necessitates exploring additional sample types. This study reports the first molecular detection of EHV-1 in ocular swabs from naturally infected horses during an outbreak in the Valencian Community in 2023. Nasal and ocular swabs were collected from ten symptomatic horses and analyzed via RT-PCR. EHV-1 was detected in all cases, with higher viral loads in nasal samples. Although nasal swabs remain the most reliable sample for EHV-1 detection, the presence of viral DNA in tear fluid suggests a previously unrecognized route of viral shedding. These findings support further investigation into the role of ocular secretions in the pathogenesis and epidemiology of EHV-1. Additional studies are needed to determine the clinical relevance and potential utility of ocular swabs in specific outbreak scenarios. Full article

(This article belongs to the Special Issue Advances in Endemic and Emerging Viral Diseases in Livestock)

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13 pages, 239 KiB

Open AccessReview

A Comparison of Vaccination Policies and Immunity Assessment for Measles Control: Insights from the United States and Japan

by Naruhito Otani, Toshiomi Okuno, Toshie Tsuchida, Kaori Ishikawa, Kaoru Ichiki, Takashi Ueda, Satoshi Higasa and Kazuhiko Nakajima

Viruses 2025, 17(6), 861; https://doi.org/10.3390/v17060861 - 17 Jun 2025

Abstract

Measles is a highly contagious viral disease and remains a global health challenge despite the availability of effective vaccines. Although many regions have successfully eliminated measles, outbreaks continue to occur owing to vaccine hesitancy, inadequate coverage, and imported cases. Differences in epidemiology, vaccination [...] Read more.

Measles is a highly contagious viral disease and remains a global health challenge despite the availability of effective vaccines. Although many regions have successfully eliminated measles, outbreaks continue to occur owing to vaccine hesitancy, inadequate coverage, and imported cases. Differences in epidemiology, vaccination policies, and immunity assessment influence measles control across countries. This paper compares measles epidemiology, vaccination policies, and immunity assessment approaches in the United States and Japan. Data were obtained from surveillance reports, national immunization programs, and peer-reviewed literature. The introduction of the measles vaccine led to substantial reductions in incidence. The United States eliminated measles in 2000 but continues to experience outbreaks due to vaccine hesitancy and imported cases. Japan implemented a two-dose policy in 2006, reducing case numbers; however, sporadic outbreaks among adults persist. In the United States, immunity is primarily assessed using documented vaccination history, whereas in Japan, enzyme immunoassay is commonly used to evaluate immunity status. Despite progress in measles elimination, achieving high vaccination coverage and addressing vaccine hesitancy remain critical challenges. Variations in immunity assessment methods impact surveillance accuracy and outbreak control. Strengthening international collaboration, standardizing assessment protocols, and enhancing public health education are crucial for sustained measles elimination. Full article

(This article belongs to the Special Issue Measles, Mumps, and Rubella)

16 pages, 1128 KiB

Open AccessArticle

Surveillance of Respiratory Pathogens Among Rapid Diagnostic Test-Negative Acute Respiratory Infection Patients in Myanmar in 2023, with a Focus on Rhinovirus and Enterovirus Genotyping

by Yuyang Sun, Tsutomu Tamura, Yadanar Kyaw, Swe Setk, Moe Myat Aye, Htay Htay Tin, Su Mon Kyaw Win, Jiaming Li, Tri Bayu Purnama, Irina Chon, Keita Wagatsuma, Hisami Watanabe and Reiko Saito

Viruses 2025, 17(6), 860; https://doi.org/10.3390/v17060860 - 17 Jun 2025

Abstract

This study explored the distribution and genetic characteristics of respiratory pathogens in outpatients with acute respiratory infections (ARIs) in Yangon, Myanmar, during the 2023 rainy season. Among 267 patients who tested negative for influenza, RSV, and SARS-CoV-2 using rapid diagnostic tests, 84.6% were [...] Read more.

This study explored the distribution and genetic characteristics of respiratory pathogens in outpatients with acute respiratory infections (ARIs) in Yangon, Myanmar, during the 2023 rainy season. Among 267 patients who tested negative for influenza, RSV, and SARS-CoV-2 using rapid diagnostic tests, 84.6% were positive for at least one pathogen according to a multiplex polymerase chain reaction (PCR) assay, the BioFire^® FilmArray^® Respiratory Panel 2.1. The most common viruses detected were rhinovirus/enterovirus (RV/EV) at 37.8%, respiratory syncytial virus (RSV) at 22.4%, and human metapneumovirus (hMPV) at 10.0%. These pathogens co-circulated mainly from July to September, with RV/EV consistently predominant. Symptom comparison among RV/EV-, RSV-, and hMPV-infected patients showed similar clinical features, though fever was more common in hMPV cases. Among RV/EV-positive patients, 59.3% had single infections, while 40.7% experienced co-infections, especially with RSV and adenovirus. Genotyping identified 28 types from five species, primarily RV-A and RV-C, which were genetically diverse. One EV-D68 case was also found, emphasizing its potential risk. This study underscores the genetic diversity and clinical impact of RV/EV and stresses the importance of ongoing molecular surveillance in Myanmar’s post-COVID-19 context to inform effective public health responses. Full article

(This article belongs to the Special Issue Influenza and Other Respiratory Viruses: Prevention, Diagnosis, Treatment: 2nd Edition)

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13 pages, 2750 KiB

Open AccessArticle

Dengue Infections Among Household Contacts of Symptomatic Index Cases: Implications for Community-Based Intervention Studies

by Erik Koehne, Liesbeth Van Wesenbeeck, Martin L. Hibberd, Annemie Buelens, Michiko Toizumi, Kim De Clerck, Leen Vijgen, Ole Lagatie, Lucy Masdin, Hien Anh Thi Nguyen, Hoang Huy Le, Duc Anh Dang, Mai Kim Huynh, Lien Thuy Le, Trieu Bao Nguyên, Stephane Hue, Hung Thai Do, Guillermo Herrera-Taracena, Freya Rasschaert and Lay-Myint Yoshida

Viruses 2025, 17(6), 859; https://doi.org/10.3390/v17060859 - 17 Jun 2025

Abstract

Background: Dengue is a global health concern, with half of the world’s population at risk and no antiviral treatment available. This Phase 0 study investigated dengue infections among household contacts (HHCs) of dengue index cases (ICs) and assessed the feasibility of conducting a [...] Read more.

Background: Dengue is a global health concern, with half of the world’s population at risk and no antiviral treatment available. This Phase 0 study investigated dengue infections among household contacts (HHCs) of dengue index cases (ICs) and assessed the feasibility of conducting a Phase 2 trial for a novel antiviral. Methods: Participants were enrolled in Nha Trang, Vietnam, from April 2022 to February 2023. Dengue ICs were identified within 72 h of fever onset, and their healthy adult HHCs enrolled within 48 h. Blood samples and questionnaires were collected bi-weekly for four weeks, with a follow-up visit on day 40. DENV RT-qPCR, NS1, and anti-DENV IgM/IgG ELISAs were performed. Results: Overall, 130 dengue ICs and 301 HHCs were enrolled, with 91.7% (276/301) completing all follow-up visits. Baseline anti-DENV IgG showed prior dengue infections in 262/301 HHCs (87.0%). Fifty HHCs were excluded from the HHC infection analysis based on evidence of a DENV infection (viral load [VL], NS1, IgM, and IgG results) at enrollment. During follow-up, 2.0% of HHCs (5/251) had DENV infections based on virological parameters (DENV RNA and/or NS1 positivity), and anti-DENV IgG/IgM seroconversion was detected in 7.2% (18/251). Conclusions: This study demonstrated the operational feasibility of a dengue IC-HHC design for a Phase 2 trial. Full article

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

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19 pages, 1819 KiB

Open AccessArticle

Rotavirus alphagastroenteritidis: Circulating Strains After the Introduction of the Rotavirus Vaccine (Rotarix^®) in Luanda Province of Angola

by Dikudila G. Vita, Cristina Santiso-Bellón, Manuel Lemos, Zoraima Neto, Elsa Fortes-Gabriel, Miguel Brito, Cruz S. Sebastião, Jesus Rodriguez-Diaz, Celso Cunha and Claudia Istrate

Viruses 2025, 17(6), 858; https://doi.org/10.3390/v17060858 - 17 Jun 2025

Abstract

Rotavirus alphagastroenteritidis (R. alphagastroenteritidis) remains the leading cause of pediatric diarrhea. Although Angola introduced Rotarix^®, the human monovalent R. alphagastroenteritidis vaccine since 2014 as part of its routine childhood immunization program, no follow-up study has been conducted. [...] Read more.

Rotavirus alphagastroenteritidis (R. alphagastroenteritidis) remains the leading cause of pediatric diarrhea. Although Angola introduced Rotarix^®, the human monovalent R. alphagastroenteritidis vaccine since 2014 as part of its routine childhood immunization program, no follow-up study has been conducted. The aim of this study was to evaluate the distribution of R. alphagastroenteritidis genotypes among children under five years of age, hospitalized with acute gastroenteritis (AGE), after the introduction of the rotavirus vaccine. To achieve this goal, stool samples collected between 2021 and 2022 from children under 5 years of age diagnosed with AGE at six hospitals in Luanda Province were analyzed. The R. alphagastroenteritidis-antigen immunochromatographic test (SD Bioline™, Abbott, Chicago, IL, USA) was performed, and 121 positive samples were genotyped. Ten samples were randomly selected for further Sanger sequencing. The results showed that the G9P[6] was the most prevalent genotype (17.3%), followed by G9P[8] (16.5%), G2P[4] (14.9%), G3P[6] (13.2%), G8P[6] (11.5%), and less frequently G12P[8] (9.1%), G1P[6] (4.1%), and G1P[8] (2.5%). The genotype combinations G3P[6], G8P[6], and G12P[8] were detected for the first time in Luanda Province. In conclusion, the emergence of new genotype combinations supports the need for continuous surveillance to identify the trend in R. alphagastroenteritidis infection and the emergence of new strains circulating in Luanda Province in the post-vaccination period. Full article

(This article belongs to the Special Issue Viruses Associated with Gastroenteritis)

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24 pages, 488 KiB

Open AccessSystematic Review

Transmission Pathways of Zoonotic Influenza Viruses and Influencing Factors: A Systematic Review of Recent Findings

by Rebecca Badra, Wenqing Zhang, John S. L. Tam, Richard Webby, Sylvie van der Werf, Sergejs Nikisins, Ann Cullinane, Saad Gharaibeh, Richard Njouom, Malik Peiris, Ghazi Kayali and Jean-Michel Heraud

Viruses 2025, 17(6), 857; https://doi.org/10.3390/v17060857 - 17 Jun 2025

Abstract

Recent outbreaks of zoonotic influenza viruses underscored the need for a deeper understanding of transmission pathways and factors influencing spillover events. Understanding the combined effects of environmental conditions, host interactions, and viral adaptations is essential for effective preparedness and response. The WHO public [...] Read more.

Recent outbreaks of zoonotic influenza viruses underscored the need for a deeper understanding of transmission pathways and factors influencing spillover events. Understanding the combined effects of environmental conditions, host interactions, and viral adaptations is essential for effective preparedness and response. The WHO public health research agenda for influenza, revised in 2017, recommended research to further define the host-to-host transmission pathways of influenza type A viruses. Since 2017, important research has been conducted, and the global health landscape has changed. Therefore, there is a need to review the transmission pathway studies conducted during the last eight years. We conducted a systematic analysis following the PRISMA guidelines on 7490 PubMed records from 2017 to 2024, of which 219 records were retained. This review evaluates research on zoonotic influenza virus transmission among wild and domestic animals and cross-species transmission to humans. By examining pathways, host, environmental, and viral factors, this review identified key findings and research gaps. Research remains limited in critical areas including transmission pathways among diverse animals, role of environmental factors, and zoonotic potential across regions. Addressing these gaps is essential for improving public health strategies. This review highlights the necessity of integrating a One Health approach in addressing zoonotic influenza risks. Full article

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

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17 pages, 1340 KiB

Open AccessArticle

Intersegment Recombination During Influenza A Virus Replication Gives Rise to a Novel Class of Defective Viral Genomes

by Soraya Anisi, George Noble, Rory Williams, Jack Hales, Hannah E. Bridgewater, Andrew Easton, William Collier and Phillip Gould

Viruses 2025, 17(6), 856; https://doi.org/10.3390/v17060856 - 16 Jun 2025

Abstract

Influenza A virus (IAV) is a highly diverse pathogen with genetic variability primarily driven by mutation and reassortment. Using next-generation sequencing (NGS), we characterised defective viral genomes (DVGs) generated during the serial passaging of influenza A/Puerto Rico/8/1934 (H1N1) virus in embryonated chicken eggs. [...] Read more.

Influenza A virus (IAV) is a highly diverse pathogen with genetic variability primarily driven by mutation and reassortment. Using next-generation sequencing (NGS), we characterised defective viral genomes (DVGs) generated during the serial passaging of influenza A/Puerto Rico/8/1934 (H1N1) virus in embryonated chicken eggs. Deletions were the most abundant DVG type, predominantly accumulating in the polymerase-encoding segments. Notably, we identified and validated a novel class of multisegment DVGs arising from intersegment recombination events, providing evidence that the IAV RNA polymerase can detach from one genomic template and resume synthesis on another. Multisegment recombination primarily involved segments 1–3 but also occurred between other segment pairings. In specific lineages, certain multisegment DVGs reached high frequencies and persisted through multiple passages, suggesting they are not transient by-products of recombination but may possess features that support stable maintenance. Furthermore, multisegment DVGs were shown to be encapsidated within virions, similar to deletion DVGs. The observation of recombination between segments with limited sequence homology underscores the potential for complex recombination to expand IAV genetic diversity. These findings suggest recombination-driven DVGs represent a previously underappreciated mechanism in influenza virus evolution. Full article

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

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12 pages, 570 KiB

Open AccessArticle

The Seroprevalence of Influenza A Virus Infections in Polish Cats During a Feline H5N1 Influenza Outbreak in 2023

by Anna Golke, Tomasz Dzieciątkowski, Olga Szaluś-Jordanow, Michał Czopowicz, Lucjan Witkowski, Monika Żychska, Ewa Domańska, Dawid Jańczak, Tomasz Nalbert, Stephanie Lesceu, Marzena Paszkowska, Justyna Giergielewicz and Tadeusz Frymus

Viruses 2025, 17(6), 855; https://doi.org/10.3390/v17060855 - 16 Jun 2025

Abstract

Recently, cats have emerged as potential incidental hosts for avian and human influenza A viruses (IAVs), including the highly pathogenic avian influenza (HPAI) H5N1 virus. Following an unprecedented outbreak of H5N1 HPAI in cats in Poland in June 2023, we conducted a cross-sectional [...] Read more.

Recently, cats have emerged as potential incidental hosts for avian and human influenza A viruses (IAVs), including the highly pathogenic avian influenza (HPAI) H5N1 virus. Following an unprecedented outbreak of H5N1 HPAI in cats in Poland in June 2023, we conducted a cross-sectional epidemiological study to assess the seroprevalence of IAV, especially H5Nx, infections in domestic cats. Eight hundred thirty-five serum samples collected in June 2023 were tested using a competitive ELISA for antibodies to IAV nucleoprotein. Positive or doubtful samples were further screened for H5-specific antibodies. The overall seropositivity for IAV was 8.5% (CI 95%: 6.8%, 10.6%; 71/835 cats), and 23/68 IAV-seropositive cats (33.8%) were also seropositive for H5 antigen. Multivariable analysis identified young age (≤8 years) and male sex as significant risk factors for H5 seropositivity, while non-H5-IAV seropositivity was more common in cats aged ≥12 years. These findings suggest different exposure pathways and host risk profiles for H5 and non-H5 IAVs and underscore the importance of enhanced surveillance in cats, particularly in regions affected by HPAI outbreaks. Given the susceptibility of cats to both avian and human IAVs, including subclinical infections, there is a theoretical risk for viral reassortment. Preventive measures, including vaccinating humans and restricting outdoor access for cats, should be considered in endemic areas. Full article

(This article belongs to the Special Issue H5N1 Influenza Viruses)

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14 pages, 2605 KiB

Open AccessArticle

Identification of Endemic Region for Severe Fever with Thrombocytopenia Syndrome in an Alluvial Plain of Hebei Province, China

by Yanan Cai, Yamei Wei, Luling Li, Minghao Geng, Yan Zheng, Xinyang Zhang, Zhanying Han, Yanbo Zhang, Yonggang Xu, Xu Han and Qi Li

Viruses 2025, 17(6), 854; https://doi.org/10.3390/v17060854 - 16 Jun 2025

Abstract

Severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious tick-borne viral disease, is increasingly affecting human beings worldwide. SFTS monitoring has been carried out since 2010 in mainland China. Since 2022, an increase in local cases has been noted in the central coastal [...] Read more.

Severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious tick-borne viral disease, is increasingly affecting human beings worldwide. SFTS monitoring has been carried out since 2010 in mainland China. Since 2022, an increase in local cases has been noted in the central coastal plain region of Hebei Province. This study aimed to identify the endemic region in the central coastal plain region by epidemiological characteristics, antibody surveillance and molecular characterization. Case data were obtained from the Chinese Disease Control and Prevention Information System. Serum samples from suspected or clinically diagnosed cases, the indigenous healthy population and native domesticated animals were collected for laboratory tests, along with ticks in the central coastal plain region of Hebei Province, China. The local cases were mainly distributed in Cangzhou City, located at the central coastal plain region of Hebei Province. The 0.68% of IgM antibody detection rate and 1.71% of IgG antibody detection rate in this study showed the potential existence of subclinical or mild infections in Cangzhou. Phylogenetic analysis indicated that all sequences from patients, ticks and sheep clustered within the F subtype, exhibiting a close evolutionary relationship and the possible circulation of SFTSV having established among animal hosts and ticks in Cangzhou. These findings first identify the natural focus of SFTSV in the central plain region of Hebei Province, highlighting enhanced surveillance measures for preventing and controlling SFTSV. Full article

(This article belongs to the Section Animal Viruses)

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16 pages, 6985 KiB

Open AccessArticle

Development of a Quadruplex RT-qPCR Assay for Rapid Detection and Differentiation of PRRSV-2 and Its Predominant Genetic Sublineages in China

by Guishan Ye, Siyu Xiong, Zhipeng Su, Guosheng Chen, Siyuan Liu, Zixuan Wang, Huanchun Chen and Anding Zhang

Viruses 2025, 17(6), 853; https://doi.org/10.3390/v17060853 - 16 Jun 2025

Abstract

Background: Porcine Reproductive and Respiratory Syndrome (PRRS) is a highly contagious disease characterized by reproductive failure in sows and severe respiratory disorders across all swine ages, causing significant economic losses. In China, the PRRSV epidemiological landscape is complex, with the coexistence of multiple [...] Read more.

Background: Porcine Reproductive and Respiratory Syndrome (PRRS) is a highly contagious disease characterized by reproductive failure in sows and severe respiratory disorders across all swine ages, causing significant economic losses. In China, the PRRSV epidemiological landscape is complex, with the coexistence of multiple lineages and frequent recombination. The major circulating strains include sublineages 1.8 (NADC30-like PRRSV) and 1.5 (NADC34-like PRRSV), along with lineages 8 (HP-like PRRSV) and 5 (VR2332-like PRRSV), highlighting the urgent need for rapid detection and lineage differentiation. Methods: A quadruplex RT-qPCR assay was developed targeting lineage-specific deletions in the NSP2 gene to simultaneously detect PRRSV-2 and differentiate NADC30-like PRRSV, HP-like PRRSV, and NADC34-like PRRSV strains. The assay was optimized with respect to reaction conditions, including annealing temperature, primers, and probe concentrations. The method’s performance was evaluated in terms of specificity, sensitivity, repeatability, stability, limit of detection (LOD), and consistency with sequencing results. Results: The assay demonstrated high sensitivity (LOD of 3 copies/μL), high specificity, and good repeatability (coefficient of variation < 1.5%). Field application using 938 samples from Guangxi A and B farms revealed NADC30-like PRRSV wild-type strains at positivity rates of 13.44% and 3.53%, respectively. Positive samples selected for sequencing were further confirmed using ORF5-based phylogenetic analysis and NSP2 deletion pattern comparison, which aligned with RT-qPCR detection results. Field application primarily detected NADC30-like PRRSV, while further validation is still needed for HP-like and NADC34-like strains. The developed quadruplex RT-qPCR assay enables rapid and simultaneous detection of PRRSV-2 and differentiation of three major lineages, providing a sensitive, specific, and reliable tool for distinguishing vaccine-derived from circulating strains and supporting targeted disease surveillance and control in swine farms. Full article

(This article belongs to the Section Animal Viruses)

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12 pages, 1358 KiB

Open AccessArticle

Persistence and Active Replication Status of Oropouche Virus in Different Body Sites: Longitudinal Analysis of a Traveler Infected with a Strain Spreading in Latin America

by Andrea Matucci, Elena Pomari, Antonio Mori, Silvia Accordini, Natasha Gianesini, Rebeca Passarelli Mantovani, Federico Giovanni Gobbi, Concetta Castilletti and Maria Rosaria Capobianchi

Viruses 2025, 17(6), 852; https://doi.org/10.3390/v17060852 - 16 Jun 2025

Abstract

An unprecedented outbreak of Oropouche virus (OROV) is occurring in the Americas, characterized by thousands of confirmed cases and a wide geographical spread, including areas outside the Amazon Basin. Little is known about this neglected arbovirus regarding its pathophysiological aspects and potentially different [...] Read more.

An unprecedented outbreak of Oropouche virus (OROV) is occurring in the Americas, characterized by thousands of confirmed cases and a wide geographical spread, including areas outside the Amazon Basin. Little is known about this neglected arbovirus regarding its pathophysiological aspects and potentially different transmission modes. This study describes the clinical course of a man who returned from a trip to Cuba and presented to our hospital 4 days after the onset of febrile symptoms. The patient was diagnosed with Oropouche fever and was followed for 177 days after the onset of symptoms. We performed a longitudinal investigation of the samples collected from several body sites (whole blood, serum, urine, and semen) with the aim of providing further insights into OROV infection dynamics, using the detection of antigenomic RNA as a marker of active viral replication. Clinical samples that were longitudinally collected over the course of OROV infection showed consistently higher amounts of antigenomic RNA compared to genomic RNA, even after viral clearance from serum. Moreover, our case study showed the persistence of OROV RNA in serum of less than 15 days from the onset of symptoms, as compared to up to one month in urine, three months in semen, and four months in whole blood. Our study suggests that Oropouche virus may persist in an actively replicating state in different body sites for long periods of time, with important implications for transmission dynamics. Furthermore, our results provide a diagnostic indication, suggesting that serum is inferior to both urine and whole blood as preferred diagnostic samples. Further studies are needed to determine the pathogenetic implications of these findings, as they have been derived from a single case and must be confirmed using a larger number of cases. Full article

(This article belongs to the Special Issue Bunyaviruses 2025)

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Graphical abstract

15 pages, 707 KiB

Open AccessSystematic Review

The Effect on Mortality of Bacterial Co-Infections on Critically Ill Patients with Community-Acquired COVID-19 and Influenza Pneumonia: A Systematic Review

by Apostolos A. Menis, Efrosyni Gerovasileiou, Konstantinos Mantzarlis, Efstratios Manoulakas, Konstantina Deskata, Vasileios Vazgiourakis, Demosthenes Makris and George Dimopoulos

Viruses 2025, 17(6), 851; https://doi.org/10.3390/v17060851 - 16 Jun 2025

Abstract

Background: Bacterial co-infections in patients with viral pneumonia might increase mortality. In this study we aimed to evaluate their effect on the mortality of critically ill patients with viral pneumonia. Methods: A systematic search was conducted in PubMed, Web of Science, Scopus and [...] Read more.

Background: Bacterial co-infections in patients with viral pneumonia might increase mortality. In this study we aimed to evaluate their effect on the mortality of critically ill patients with viral pneumonia. Methods: A systematic search was conducted in PubMed, Web of Science, Scopus and Cochrane from inception until 30 March 2025. We included studies comparing the effect on mortality of bacterial co-infections in critically ill patients with viral pneumonia. The risk of bias was assessed by the Newcastle–Ottawa Scale. Results: From 3643 studies, 10 were included in our study with a total of 2862 COVID-19 patients and 4573 influenza patients. Seven studies were retrospective and three prospective. In total, 359/2862 of the COVID-19 and 904/4573 of the influenza patients were co-infected. Co-infections increased mortality in five out of the six studies evaluating COVID-19 patients and in two out of the eight studies evaluating influenza patients. Conclusions: The majority of the included studies were retrospective, which may limit the accuracy of these results. The exclusion of non-English literature may have led to the omission of relevant data. Based on our results, the impact of bacterial co-infection may be more pronounced in patients with COVID-19 pneumonia admitted to the ICU than in patients with influenza pneumonia. Full article

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

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18 pages, 2588 KiB

Open AccessReview

Integrative Computational Approaches for Understanding Drug Resistance in HIV-1 Protease Subtype C

by Sankaran Venkatachalam, Nisha Muralidharan, Ramesh Pandian, Yasien Sayed and M. Michael Gromiha

Viruses 2025, 17(6), 850; https://doi.org/10.3390/v17060850 - 16 Jun 2025

Abstract

Acquired immunodeficiency syndrome (AIDS) is a chronic disease condition caused by the human immunodeficiency virus (HIV). The widespread availability of highly active antiretroviral therapies has helped to control HIV. There are ten FDA-approved protease inhibitors (PIs) that are used as part of antiretroviral [...] Read more.

Acquired immunodeficiency syndrome (AIDS) is a chronic disease condition caused by the human immunodeficiency virus (HIV). The widespread availability of highly active antiretroviral therapies has helped to control HIV. There are ten FDA-approved protease inhibitors (PIs) that are used as part of antiretroviral therapies in HIV treatment. Importantly, all these drugs are designed and developed against the protease (PR) from HIV subtype B. On the other hand, HIV-1 PR subtype C, which is the most dominant strain in countries including South Africa and India, has shown resistance to PIs due to its genetic diversity and varied mutations. The emergence of resistance is concerning because the virus continues to replicate despite treatment; hence, it is necessary to develop drugs specifically against subtype C. This review focuses on the origin, genetic diversity, and mutations associated with HIV-1 PR subtype C. Furthermore, computational studies performed on HIV-1 PR subtype C and mutations associated with its resistance to PIs are highlighted. Moreover, potential research gaps and future directions in the study of HIV-1 PR subtype C are discussed. Full article

(This article belongs to the Special Issue HIV Protease)

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