Viruses

46 pages, 1596 KiB

Open AccessReview

The Immune System—A Double-Edged Sword for Adenovirus-Based Therapies

by Rebecca Wallace, Carly M. Bliss and Alan L. Parker

Viruses 2024, 16(6), 973; https://doi.org/10.3390/v16060973 - 17 Jun 2024

Pathogenic adenovirus (Ad) infections are widespread but typically mild and transient, except in the immunocompromised. As vectors for gene therapy, vaccine, and oncology applications, Ad-based platforms offer advantages, including ease of genetic manipulation, scale of production, and well-established safety profiles, making them attractive [...] Read more.

Pathogenic adenovirus (Ad) infections are widespread but typically mild and transient, except in the immunocompromised. As vectors for gene therapy, vaccine, and oncology applications, Ad-based platforms offer advantages, including ease of genetic manipulation, scale of production, and well-established safety profiles, making them attractive tools for therapeutic development. However, the immune system often poses a significant challenge that must be overcome for adenovirus-based therapies to be truly efficacious. Both pre-existing anti-Ad immunity in the population as well as the rapid development of an immune response against engineered adenoviral vectors can have detrimental effects on the downstream impact of an adenovirus-based therapeutic. This review focuses on the different challenges posed, including pre-existing natural immunity and anti-vector immunity induced by a therapeutic, in the context of innate and adaptive immune responses. We summarise different approaches developed with the aim of tackling these problems, as well as their outcomes and potential future applications. Full article

(This article belongs to the Special Issue 15th International Adenovirus Meeting)

45 pages, 712 KiB

Open AccessReview

Making a Monkey out of Human Immunodeficiency Virus/Simian Immunodeficiency Virus Pathogenesis: Immune Cell Depletion Experiments as a Tool to Understand the Immune Correlates of Protection and Pathogenicity in HIV Infection

by Jen Symmonds, Thaidra Gaufin, Cuiling Xu, Kevin D. Raehtz, Ruy M. Ribeiro, Ivona Pandrea and Cristian Apetrei

Viruses 2024, 16(6), 972; https://doi.org/10.3390/v16060972 - 17 Jun 2024

Abstract

Understanding the underlying mechanisms of HIV pathogenesis is critical for designing successful HIV vaccines and cure strategies. However, achieving this goal is complicated by the virus’s direct interactions with immune cells, the induction of persistent reservoirs in the immune system cells, and multiple [...] Read more.

Understanding the underlying mechanisms of HIV pathogenesis is critical for designing successful HIV vaccines and cure strategies. However, achieving this goal is complicated by the virus’s direct interactions with immune cells, the induction of persistent reservoirs in the immune system cells, and multiple strategies developed by the virus for immune evasion. Meanwhile, HIV and SIV infections induce a pandysfunction of the immune cell populations, making it difficult to untangle the various concurrent mechanisms of HIV pathogenesis. Over the years, one of the most successful approaches for dissecting the immune correlates of protection in HIV/SIV infection has been the in vivo depletion of various immune cell populations and assessment of the impact of these depletions on the outcome of infection in non-human primate models. Here, we present a detailed analysis of the strategies and results of manipulating SIV pathogenesis through in vivo depletions of key immune cells populations. Although each of these methods has its limitations, they have all contributed to our understanding of key pathogenic pathways in HIV/SIV infection. Full article

(This article belongs to the Special Issue Simian Immunodeficiency Virus Models of HIV/AIDS in Nonhuman Primates 2024)

29 pages, 408 KiB

Open AccessReview

The Impact of Drugs and Substance Abuse on Viral Pathogenesis—A South African Perspective

by Lufuno Ratshisusu, Omphile Elizabeth Simani, Jason T. Blackard and Selokela G. Selabe

Viruses 2024, 16(6), 971; https://doi.org/10.3390/v16060971 - 17 Jun 2024

Abstract

Illicit drug and alcohol abuse have significant negative consequences for individuals who inject drugs/use drugs (PWID/UDs), including decreased immune system function and increased viral pathogenesis. PWID/UDs are at high risk of contracting or transmitting viral illnesses such as human immunodeficiency virus (HIV), hepatitis [...] Read more.

Illicit drug and alcohol abuse have significant negative consequences for individuals who inject drugs/use drugs (PWID/UDs), including decreased immune system function and increased viral pathogenesis. PWID/UDs are at high risk of contracting or transmitting viral illnesses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). In South Africa, a dangerous drug-taking method known as “Bluetoothing” has emerged among nyaope users, whereby the users of this drug, after injecting, withdraw blood from their veins and then reinject it into another user. Hence, the transmission of blood-borne viruses (BBVs) is exacerbated by this “Bluetooth” practice among nyaope users. Moreover, several substances of abuse promote HIV, HBV, and HCV replication. With a specific focus on the nyaope drug, viral replication, and transmission, we address the important influence of abused addictive substances and polysubstance use in this review. Full article

(This article belongs to the Special Issue HIV and Drugs of Abuse, 3rd Edition)

12 pages, 1082 KiB

Open AccessReview

The Role of Satellites in the Evolution of Begomoviruses

by Anupam Varma and Manoj Kumar Singh

Viruses 2024, 16(6), 970; https://doi.org/10.3390/v16060970 - 17 Jun 2024

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Abstract

Begomoviruses have emerged as destructive pathogens of crops, particularly in the tropics and subtropics, causing enormous economic losses and threatening food security. Epidemics caused by begomoviruses have even spread in regions and crops that were previously free from these viruses. The most seriously [...] Read more.

Begomoviruses have emerged as destructive pathogens of crops, particularly in the tropics and subtropics, causing enormous economic losses and threatening food security. Epidemics caused by begomoviruses have even spread in regions and crops that were previously free from these viruses. The most seriously affected crops include cassava; cotton; grain legumes; and cucurbitaceous, malvaceous, and solanaceous vegetables. Alphasatellites, betasatellites, and deltasatellites are associated with the diseases caused by begomoviruses, but begomovirus–betasatellite complexes have played significant roles in the evolution of begomoviruses, causing widespread epidemics in many economically important crops throughout the world. This article provides an overview of the evolution, distribution, and approaches used by betasatellites in the suppression of host plant defense responses and increasing disease severity. Full article

(This article belongs to the Special Issue Viroids and Satellites and Their Vector Interactions—This Special Issue Is Dedicated to the Memory of Theodor O. Diener Who Discovered Viroids)

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14 pages, 3668 KiB

Open AccessArticle

Identification and Genomic Characterization of Two Novel Hepatoviruses in Shrews from Yunnan Province, China

by Yi Tang, Kai Zhao, Hong-Min Yin, Li-Ping Yang, Yue-Chun Wu, Feng-Yi Li, Ze Yang, Hui-Xuan Lu, Bo Wang, Yin Yang, Yun-Zhi Zhang and Xing-Lou Yang

Viruses 2024, 16(6), 969; https://doi.org/10.3390/v16060969 - 17 Jun 2024

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Abstract

Hepatitis A virus (HAV), a member of the genus Hepatovirus (Picornaviridae HepV), remains a significant viral pathogen, frequently causing enterically transmitted hepatitis worldwide. In this study, we conducted an epidemiological survey of HepVs carried by small terrestrial mammals in the wild in [...] Read more.

Hepatitis A virus (HAV), a member of the genus Hepatovirus (Picornaviridae HepV), remains a significant viral pathogen, frequently causing enterically transmitted hepatitis worldwide. In this study, we conducted an epidemiological survey of HepVs carried by small terrestrial mammals in the wild in Yunnan Province, China. Utilizing HepV-specific broad-spectrum RT-PCR, next-generation sequencing (NGS), and QNome nanopore sequencing (QNS) techniques, we identified and characterized two novel HepVs provisionally named EpMa-HAV and EpLe-HAV, discovered in the long-tailed mountain shrew (Episoriculus macrurus) and long-tailed brown-toothed shrew (Episoriculus leucops), respectively. Our sequence and phylogenetic analyses of EpMa-HAV and EpLe-HAV indicated that they belong to the species Hepatovirus I (HepV-I) clade II, also known as the Chinese shrew HepV clade. Notably, the codon usage bias pattern of novel shrew HepVs is consistent with that of previously identified Chinese shrew HepV. Furthermore, our structural analysis demonstrated that shrew HepVs differ from other mammalian HepVs in RNA secondary structure and exhibit variances in key protein sites. Overall, the discovery of two novel HepVs in shrews expands the host range of HepV and underscores the existence of genetically diverse animal homologs of human HAV within the genus HepV. Full article

(This article belongs to the Special Issue Human Hepatitis Viruses and Their Animal Homologues)

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3 pages, 444 KiB

Open AccessEditorial

Phage Display in Cancer Research: Special Issue Editorial

by Valery A. Petrenko

Viruses 2024, 16(6), 968; https://doi.org/10.3390/v16060968 - 17 Jun 2024

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Abstract

Soon after its birth in 1985, following a short lag period [...] Full article

(This article belongs to the Special Issue Phage Display in Cancer Research)

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14 pages, 877 KiB

Open AccessArticle

Neurological Manifestations of Acute SARS-CoV-2 Infection in Pediatric Patients: A 3-Year Study on Differences between Pandemic Waves

by Iolanda Cristina Vivisenco, Andreea Lescaie, Ana Dragomirescu, Ioana Cătălina Ioniță, Irina Florescu, Bogdan Ciocea, Andreea Rodica Grama, Maria-Dorina Crăciun, Carmen-Daniela Chivu, Coriolan Emil Ulmeanu and Viorela Gabriela Nițescu

Viruses 2024, 16(6), 967; https://doi.org/10.3390/v16060967 - 17 Jun 2024

Viewed by 258

Abstract

This study analyzed the neurological manifestation profiles of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across pandemic waves in pediatric patients. The study collected data on patients aged between 0 and 18 years, diagnosed with acute SARS-CoV-2 infection, admitted to a pediatric [...] Read more.

This study analyzed the neurological manifestation profiles of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across pandemic waves in pediatric patients. The study collected data on patients aged between 0 and 18 years, diagnosed with acute SARS-CoV-2 infection, admitted to a pediatric tertiary hospital between 1 March 2020 and 28 February 2023. This study included 1677 patients. Neurological manifestations were noted in 10% (n = 168) of patients with a median age of 3.2 years (interquartile range: 1–11.92). Neurological manifestations were significantly associated with the pandemic waves (p = 0.006) and age groups (p < 0.001). Seizures were noted in 4.2% of cases and reached an increasing frequency over time (p = 0.001), but were not associated with age groups. Febrile seizures accounted for the majority of seizures. Headache was reported in 2.6% of cases and had similar frequencies across the pandemic waves and age groups. Muscular involvement was noted in 2% of cases, reached a decreasing frequency over time (p < 0.001), and showed different frequencies among the age groups. Neurological manifestations of acute SARS-CoV-2 infection exhibit distinct patterns, depending on the pandemic wave and patient age group. The Wuhan and Omicron waves involved the nervous system more often than the other waves. Full article

(This article belongs to the Special Issue COVID-19 Complications and Co-infections)

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13 pages, 1194 KiB

Open AccessReview

Nucleic Acid Sensor-Mediated PANoptosis in Viral Infection

by Lili Zhu, Zehong Qi, Huali Zhang and Nian Wang

Viruses 2024, 16(6), 966; https://doi.org/10.3390/v16060966 - 16 Jun 2024

Viewed by 326

Abstract

Innate immunity, the first line of host defense against viral infections, recognizes viral components through different pattern-recognition receptors. Nucleic acids derived from viruses are mainly recognized by Toll-like receptors, nucleotide-binding domain leucine-rich repeat-containing receptors, absent in melanoma 2-like receptors, and cytosolic DNA sensors [...] Read more.

Innate immunity, the first line of host defense against viral infections, recognizes viral components through different pattern-recognition receptors. Nucleic acids derived from viruses are mainly recognized by Toll-like receptors, nucleotide-binding domain leucine-rich repeat-containing receptors, absent in melanoma 2-like receptors, and cytosolic DNA sensors (e.g., Z-DNA-binding protein 1 and cyclic GMP-AMP synthase). Different types of nucleic acid sensors can recognize specific viruses due to their unique structures. PANoptosis is a unique form of inflammatory cell death pathway that is triggered by innate immune sensors and driven by caspases and receptor-interacting serine/threonine kinases through PANoptosome complexes. Nucleic acid sensors (e.g., Z-DNA-binding protein 1 and absent in melanoma 2) not only detect viruses, but also mediate PANoptosis through providing scaffold for the assembly of PANoptosomes. This review summarizes the structures of different nucleic acid sensors, discusses their roles in viral infections by driving PANoptosis, and highlights the crosstalk between different nucleic acid sensors. It also underscores the promising prospect of manipulating nucleic acid sensors as a therapeutic approach for viral infections. Full article

(This article belongs to the Special Issue PANoptosis in Viral Infection)

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17 pages, 6449 KiB

Open AccessArticle

Isolation and Characterization of Contemporary Bovine Coronavirus Strains

by Yu Li, Roberto A. Palomares, Mingde Liu, Jiayu Xu, Chohee Koo, Francesca Granberry, Samantha R. Locke, Greg Habing, Linda J. Saif, Leyi Wang and Qiuhong Wang

Viruses 2024, 16(6), 965; https://doi.org/10.3390/v16060965 - 16 Jun 2024

Viewed by 324

Abstract

Bovine coronavirus (BCoV) poses a threat to cattle health worldwide, contributing to both respiratory and enteric diseases. However, few contemporary strains have been isolated. In this study, 71 samples (10 nasal and 61 fecal) were collected from one farm in Ohio in 2021 [...] Read more.

Bovine coronavirus (BCoV) poses a threat to cattle health worldwide, contributing to both respiratory and enteric diseases. However, few contemporary strains have been isolated. In this study, 71 samples (10 nasal and 61 fecal) were collected from one farm in Ohio in 2021 and three farms in Georgia in 2023. They were screened by BCoV-specific real-time reverse transcription-PCR, and 15 BCoV-positive samples were identified. Among them, five BCoV strains from fecal samples were isolated using human rectal tumor-18 (HRT-18) cells. The genomic sequences of five strains were obtained. The phylogenetic analysis illustrated that these new strains clustered with US BCoVs that have been detected since the 1990s. Sequence analyses of the spike proteins of four pairs of BCoVs, with each pair originally collected from the respiratory and enteric sites of one animal, revealed the potential amino acid residue patterns, such as D1180 for all four enteric BCoVs and G1180 for three of four respiratory BCoVs. This project provides new BCoV isolates and sequences and underscores the genetic diversity of BcoVs, the unknown mechanisms of disease types, and the necessity of sustained surveillance and research for BCoVs. Full article

(This article belongs to the Section Coronaviruses)

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16 pages, 2426 KiB

Open AccessArticle

Molecular Detection and Genetic Characterization of Two Dugbe Orthonairovirus Isolates Detected from Ticks in Southern Senegal

by Mignane Ndiaye, Aminata Badji, Idrissa Dieng, Anna S. Dolgova, Moufid Mhamadi, Anastasiia D. Kirichenko, Anna S. Gladkikh, Alioune Gaye, Ousmane Faye, Amadou Alpha Sall, Mawlouth Diallo, Vladimir G. Dedkov and Oumar Faye

Viruses 2024, 16(6), 964; https://doi.org/10.3390/v16060964 - 15 Jun 2024

Viewed by 232

Abstract

Dugbe virus (DUGV) is a tick-borne arbovirus first isolated in Nigeria in 1964. It has been detected in many African countries using such diverse methods as serological tests, virus isolation, and molecular detection. In Senegal, reports of DUGV isolates mainly occurred in the [...] Read more.

Dugbe virus (DUGV) is a tick-borne arbovirus first isolated in Nigeria in 1964. It has been detected in many African countries using such diverse methods as serological tests, virus isolation, and molecular detection. In Senegal, reports of DUGV isolates mainly occurred in the 1970s and 1980s. Here, we report a contemporary detection of three novel DUGV isolates upon screening of a total of 2877 individual ticks regrouped into 844 pools. The three positive pools were identified as Amblyomma variegatum, the main known vector of DUGV, collected in the southern part of the country (Kolda region). Interestingly, phylogenetic analysis indicates that the newly sequenced isolates are globally related to the previously characterized isolates in West Africa, thus highlighting potentially endemic, unnoticed viral transmission. This study was also an opportunity to develop a rapid and affordable protocol for full-genome sequencing of DUGV using nanopore technology. The results suggest a relatively low mutation rate and relatively conservative evolution of DUGV isolates. Full article

(This article belongs to the Special Issue Virus Discovery, Classification and Characterization)

10 pages, 764 KiB

Open AccessArticle

Torquetenovirus Viremia Quantification Using Real-Time PCR Developed on a Fully Automated, Random-Access Platform

by Pietro Giorgio Spezia, Fabrizio Carletti, Federica Novazzi, Eliana Specchiarello, Angelo Genoni, Francesca Drago Ferrante, Claudia Minosse, Giulia Matusali, Nicasio Mancini, Daniele Focosi, Guido Antonelli, Enrico Girardi and Fabrizio Maggi

Viruses 2024, 16(6), 963; https://doi.org/10.3390/v16060963 - 15 Jun 2024

Viewed by 193

Abstract

Quantification of Torquetenovirus (TTV) viremia is becoming important for evaluating the status of the immune system in solid organ transplant recipients, monitoring the appearance of post-transplant complications, and controlling the efficacy of maintenance immunosuppressive therapy. Thus, diagnostic approaches able to scale up TTV [...] Read more.

Quantification of Torquetenovirus (TTV) viremia is becoming important for evaluating the status of the immune system in solid organ transplant recipients, monitoring the appearance of post-transplant complications, and controlling the efficacy of maintenance immunosuppressive therapy. Thus, diagnostic approaches able to scale up TTV quantification are needed. Here, we report on the development and validation of a real-time PCR assay for TTV quantification on the Hologic Panther Fusion^® System by utilizing its open-access channel. The manual real-time PCR previously developed in our laboratories was optimized to detect TTV DNA on the Hologic Panther Fusion^® System. The assay was validated using clinical samples. The automated TTV assay has a limit of detection of 1.6 log copies per ml of serum. Using 112 samples previously tested via manual real-time PCR, the concordance in TTV detection was 93% between the assays. When the TTV levels were compared, the overall agreement between the methods, as assessed using Passing–Bablok linear regression and Bland–Altman analyses, was excellent. In summary, we validated a highly sensitive and accurate method for the diagnostic use of TTV quantification on a fully automated Hologic Panther Fusion^® System. This will greatly improve the turnaround time for TTV testing and better support the laboratory diagnosis of this new viral biomarker. Full article

(This article belongs to the Special Issue Advancing Research of Anelloviruses)

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18 pages, 1525 KiB

Open AccessArticle

Human Immunodeficiency Virus Type-1 Genetic Diversity and Drugs Resistance Mutations among People Living with HIV in Karachi, Pakistan

by Abdur Rashid, Li Kang, Feng Yi, Qingfei Chu, Sharaf Ali Shah, Syed Faisal Mahmood, Yimam Getaneh, Min Wei, Song Chang, Syed Hani Abidi and Yiming Shao

Viruses 2024, 16(6), 962; https://doi.org/10.3390/v16060962 - 14 Jun 2024

Viewed by 250

Abstract

The human immunodeficiency virus type-1 epidemic in Pakistan has significantly increased over the last two decades. In Karachi, Pakistan, there is a lack of updated information on the complexity of HIV-1 genetic diversity and the burden of drug resistance mutations (DRMs) that can [...] Read more.

The human immunodeficiency virus type-1 epidemic in Pakistan has significantly increased over the last two decades. In Karachi, Pakistan, there is a lack of updated information on the complexity of HIV-1 genetic diversity and the burden of drug resistance mutations (DRMs) that can contribute to ART failure and poor treatment outcomes. This study aimed to determine HIV-1 genetic diversity and identify drug-resistance mutations among people living with HIV in Karachi. A total of 364 HIV-positive individuals, with a median age of 36 years, were enrolled in the study. The HIV-1 partial pol gene was successfully sequenced from 268 individuals. The sequences were used to generate phylogenetic trees to determine clade diversity and also to assess the burden of DRMs. Based on the partial pol sequences, 13 distinct HIV-1 subtypes and recombinant forms were identified. Subtype A1 was the most common clade (40%), followed by CRF02_AG (33.2%). Acquired DRMs were found in 30.6% of the ART-experienced patients, of whom 70.7%, 20.7%, and 8.5% were associated with resistance to NNRTIs, NRTIs, and PIs, respectively. Transmitted DRMs were found in 5.6% of the ART-naïve patients, of whom 93% were associated with resistance against NNRTIs and 7% to PIs. The high prevalence of DRMs in ART-experienced patients poses significant challenges to the long-term benefits and sustainability of the ART program. This study emphasizes the importance of continuous HIV molecular epidemiology and drug resistance surveillance to support evidence-based HIV prevention, precise ART, and targeted AIDS care. Full article

(This article belongs to the Special Issue The Challenge of HIV Diversity)

14 pages, 2190 KiB

Open AccessArticle

Application of MPBT Assay for Multiplex Determination of Infectious Titers and for Selection of the Optimal Formulation for the Trivalent Novel Oral Poliovirus Vaccine

by Hasmik Manukyan, Manjari Lal, Changcheng Zhu, Olga Singh, Tsai-Lien Lin, Erman Tritama, Konstantin Chumakov, Shwu-Maan Lee and Majid Laassri

Viruses 2024, 16(6), 961; https://doi.org/10.3390/v16060961 - 14 Jun 2024

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Abstract

Recently, a multiplex PCR-based titration (MPBT) assay was developed for simultaneous determination of infectious titers of all three Sabin strains of the oral poliovirus vaccine (OPV) to replace the conventional CCID₅₀ assay, which is both time-consuming and laborious. The MPBT assay was [...] Read more.

Recently, a multiplex PCR-based titration (MPBT) assay was developed for simultaneous determination of infectious titers of all three Sabin strains of the oral poliovirus vaccine (OPV) to replace the conventional CCID₅₀ assay, which is both time-consuming and laborious. The MPBT assay was shown to be reproducible, robust and sensitive. The conventional and MPBT assays showed similar results and sensitivity. The MPBT assay can be completed in two to three days, instead of ten days for the conventional assay. To prevent attenuated vaccine strains of poliovirus from reversion to virulence, a novel, genetically stable OPV (nOPV) was developed by modifying the genomes of conventional Sabin strains used in OPV. In this work, we evaluated the MPBT assay as a rapid screening tool to support trivalent nOPV (tnOPV) formulation development by simultaneous titration of the three nOPV strains to confirm stability as needed, for the selection of the lead tnOPV formulation candidate. We first assessed the ability of the MPBT assay to discriminate a 0.5 log₁₀ titer difference by titrating the two tnOPV samples (undiluted and threefold-diluted) on the same plate. Once the assay was shown to be discriminating, we then tested different formulations of tnOPV drug products (DPs) that were subjected to different exposure times at 37 °C (untreated group and treated groups: 2 and 7 days at 37 °C), and to three freeze and thaw (FT) cycles. Final confirmation of the down selected formulation candidates was achieved by performing the conventional CCID₅₀ assay, comparing the stability of untreated and treated groups and FT stability testing on the top three candidates. The results showed that the MPBT assay generates similar titers as the conventional assay. By testing two trivalent samples in the same plate, the assay can differentiate a 0.5 log₁₀ difference between the titers of the tested nOPV samples. Also, the assay was able to detect the gradual degradation of nOPV viruses with different formulation compositions and under different time/temperature conditions and freeze/thaw cycles. We found that there were three tnOPV formulations which met the stability criteria of less than 0.5 log₁₀ loss after 2 days’ exposure to 37 ℃ and after three FT cycles, maintaining the potency of all three serotypes in these formulations. The ability of the MPBT assay to titrate two tnOPV lots (six viruses) in the same plate makes it cheaper and gives it a higher throughput for rapid screening. The assay detected the gradual degradation of the tnOPV and was successful in the selection of optimal formulations for the tnOPV. The results demonstrated that the MPBT method can be used as a stability indicating assay to assess the thermal stability of the nOPV. It can be used for rapid virus titer determination during the vaccine manufacturing process, and in clinical trials. The MPBT assay can be automated and applied for other viruses, including those with no cytopathic effect. Full article

(This article belongs to the Special Issue An Update on Enterovirus Research)

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14 pages, 1013 KiB

Open AccessReview

Exploring Iguape Virus—A Lesser-Known Orthoflavivirus

by Marielena V. Saivish, Maurício L. Nogueira, Shannan L. Rossi and Nikos Vasilakis

Viruses 2024, 16(6), 960; https://doi.org/10.3390/v16060960 - 14 Jun 2024

Viewed by 489

Abstract

Brazil has earned the moniker “arbovirus hotspot”, providing an ideal breeding ground for a multitude of arboviruses thriving in various zoonotic and urban cycles. As the planet warms and vectors expand their habitat range, a nuanced understanding of lesser-known arboviruses and the factors [...] Read more.

Brazil has earned the moniker “arbovirus hotspot”, providing an ideal breeding ground for a multitude of arboviruses thriving in various zoonotic and urban cycles. As the planet warms and vectors expand their habitat range, a nuanced understanding of lesser-known arboviruses and the factors that could drive their emergence becomes imperative. Among these viruses is the Iguape virus (IGUV), a member of the Orthoflavivirus aroaense species, which was first isolated in 1979 from a sentinel mouse in the municipality of Iguape, within the Vale do Ribeira region of São Paulo State. While evidence suggests that IGUV circulates among birds, wild rodents, marsupials, bats, and domestic birds, there is no information available on its pathogenesis in both humans and animals. The existing literature on IGUV spans decades, is outdated, and is often challenging to access. In this review, we have curated information from the known literature, clarifying its elusive nature and investigating the factors that may influence its emergence. As an orthoflavivirus, IGUV poses a potential threat, which demands our attention and vigilance, considering the serious outbreaks that the Zika virus, another neglected orthoflavivirus, has unleashed in the recent past. Full article

(This article belongs to the Special Issue Zoonotic and Vector-Borne Viral Diseases)

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10 pages, 279 KiB

Open AccessBrief Report

Antiviral Activity of Ag₅IO_6,A Unique Silver Compound

by Mauri Erickson, Tyler J. Boone and Patricia L. Nadworny

Viruses 2024, 16(6), 959; https://doi.org/10.3390/v16060959 - 13 Jun 2024

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Abstract

Pentasilver hexaoxoiodate (Ag₅IO₆) has broad-spectrum antimicrobial efficacy, including the long-term prevention of microbial adherence, the rapid killing of planktonic microorganisms, and the elimination of mature biofilms. This study’s goal was to determine whether it may also have antiviral activity [...] Read more.

Pentasilver hexaoxoiodate (Ag₅IO₆) has broad-spectrum antimicrobial efficacy, including the long-term prevention of microbial adherence, the rapid killing of planktonic microorganisms, and the elimination of mature biofilms. This study’s goal was to determine whether it may also have antiviral activity against structurally distinct viruses. Ag₅IO₆ was tested following ASTM E1052-20, Standard Practice to Assess the Activity of Microbicides Against Viruses in Suspension, against adenovirus type 5, murine norovirus, poliovirus type 1, SARS-CoV-2 (original), and SARS-CoV-2 (omicron) (host cells: H1HeLa, RAW 264.7, LLC-MK2, Vero E6, and Vero E6, respectively). A 0.1 g/mL Ag₅IO₆ suspension was prepared and the viruses were exposed for 30 min, 4 h, or 24 h. Exposure to Ag₅IO₆ resulted in complete kill of SARS-CoV-2 (omicron) within 30 min, as well as complete kill of both SARS-CoV-2 (original) and the murine norovirus within 4 h. Ag₅IO₆ showed increasing activity over time against the adenovirus, but did not achieve a 3-log reduction within 24 h, and showed no antiviral activity against the poliovirus. These results demonstrate that Ag₅IO₆ has antiviral activity against medically important viruses, in addition to its well-characterized antimicrobial activity, suggesting that it may be valuable in situations where the prevention or simultaneous treatment of microbes and viruses are necessary. Full article

(This article belongs to the Special Issue Impact of Co-infections in COVID-19: Predisposing Mechanisms and Interplay between Invasive Viral, Bacterial and Fungal Pathogens)

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28 pages, 6709 KiB

Open AccessArticle

Epidemiological and Genetic Characteristics of Respiratory Viral Coinfections with Different Variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

by Ivelina Trifonova, Neli Korsun, Iveta Madzharova, Ivailo Alexiev, Ivan Ivanov, Viktoria Levterova, Lyubomira Grigorova, Ivan Stoikov, Dean Donchev and Iva Christova

Viruses 2024, 16(6), 958; https://doi.org/10.3390/v16060958 - 13 Jun 2024

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Abstract

This study aimed to determine the incidence and etiological, seasonal, and genetic characteristics of respiratory viral coinfections involving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Between October 2020 and January 2024, nasopharyngeal samples were collected from 2277 SARS-CoV-2-positive patients. Two multiplex approaches were [...] Read more.

This study aimed to determine the incidence and etiological, seasonal, and genetic characteristics of respiratory viral coinfections involving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Between October 2020 and January 2024, nasopharyngeal samples were collected from 2277 SARS-CoV-2-positive patients. Two multiplex approaches were used to detect and sequence SARS-CoV-2, influenza A/B viruses, and other seasonal respiratory viruses: multiplex real-time polymerase chain reaction (PCR) and multiplex next-generation sequencing. Coinfections of SARS-CoV-2 with other respiratory viruses were detected in 164 (7.2%) patients. The most common co-infecting virus was respiratory syncytial virus (RSV) (38 cases, 1.7%), followed by bocavirus (BoV) (1.2%) and rhinovirus (RV) (1.1%). Patients ≤ 16 years of age had the highest rate (15%) of mixed infections. Whole-genome sequencing produced 19 complete genomes of seasonal respiratory viral co-pathogens, which were subjected to phylogenetic and amino acid analyses. The detected influenza viruses were classified into the genetic groups 6B.1A.5a.2a and 6B.1A.5a.2a.1 for A(H1N1)pdm09, 3C.2a1b.2a.2a.1 and 3C.2a.2b for A(H3N2), and V1A.3a.2 for the B/Victoria lineage. The RSV-B sequences belonged to the genetic group GB5.0.5a, with HAdV-C belonging to type 1, BoV to genotype VP1, and PIV3 to lineage 1a(i). Multiple amino acid substitutions were identified, including at the antibody-binding sites. This study provides insights into respiratory viral coinfections involving SARS-CoV-2 and reinforces the importance of genetic characterization of co-pathogens in the development of therapeutic and preventive strategies. Full article

(This article belongs to the Special Issue The Influence of COVID-19 Pandemic on the Epidemiology of Other Human Viral Infections)

14 pages, 400 KiB

Open AccessArticle

Hepatitis C (HCV) Reinfection and Risk Factors among Clients of a Low-Threshold Primary Healthcare Service for People Who Inject Drugs in Sydney, Australia

by Phillip Read, Bruce Zi Huan Tang, Edmund Silins, Anna Doab, Vincent J. Cornelisse and Rosie Gilliver

Viruses 2024, 16(6), 957; https://doi.org/10.3390/v16060957 - 13 Jun 2024

Viewed by 233

Abstract

Hepatitis C (HCV) reinfection studies have not focused on primary healthcare services in Australia, where priority populations including people who inject drugs (PWID) typically engage in healthcare. We aimed to describe the incidence of HCV reinfection and associated risk factors in a cohort [...] Read more.

Hepatitis C (HCV) reinfection studies have not focused on primary healthcare services in Australia, where priority populations including people who inject drugs (PWID) typically engage in healthcare. We aimed to describe the incidence of HCV reinfection and associated risk factors in a cohort of people most at risk of reinfection in a real-world community setting. We conducted a secondary analysis of routinely collected HCV testing and treatment data from treatment episodes initiated with direct-acting antiviral (DAA) therapy between October 2015 and June 2021. The overall proportion of clients (N = 413) reinfected was 9% (N = 37), and the overall incidence rate of HCV reinfection was 9.5/100PY (95% CI: 6.3–14.3). Reinfection incidence rates varied by sub-group and were highest for Aboriginal and/or Torres Strait Islander people (20.4/100PY; 95% CI: 12.1–34.4). Among PWID (N= 321), only Aboriginality was significantly associated with reinfection (AOR: 2.73, 95% CI: 1.33–5.60, p = 0.006). High rates of HCV reinfection in populations with multiple vulnerabilities and continued drug use, especially among Aboriginal and Torres Strait Islander people, highlight the need for ongoing regular HCV testing and retreatment in order to achieve HCV elimination. A priority is resourcing testing and treatment for Aboriginal and/or Torres Strait Islander people. Our findings support the need for novel and holistic healthcare strategies for PWID and the upscaling of Indigenous cultural approaches and interventions. Full article

(This article belongs to the Special Issue Hepatitis C Virus Infection among People Who Inject Drugs)

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12 pages, 1028 KiB

Open AccessReview

Breaking the Barrier: SARS-CoV-2 Infections in Wild and Companion Animals and Their Implications for Public Health

by Zhandos Abay, Sandugash Sadikaliyeva, Ainur Nurpeisova, Kuanysh Jekebekov, Kamshat Shorayeva, Bolat Yespembetov, Sergazy Nurabayev, Aslan Kerimbayev, Berik Khairullin, Hansang Yoo, Lespek Kutumbetov, Markhabat Kassenov and Kunsulu Zakarya

Viruses 2024, 16(6), 956; https://doi.org/10.3390/v16060956 - 13 Jun 2024

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Abstract

The emergence of the novel coronavirus SARS-CoV-2 has led to significant interest in its potential transmission between animals and humans, especially pets. This review article summarises the literature on coronavirus infections in domestic animals, emphasising epidemiology, transmission dynamics, clinical manifestations, and public health [...] Read more.

The emergence of the novel coronavirus SARS-CoV-2 has led to significant interest in its potential transmission between animals and humans, especially pets. This review article summarises the literature on coronavirus infections in domestic animals, emphasising epidemiology, transmission dynamics, clinical manifestations, and public health implications. This article highlights current understandings of the relationship between infections in companion animals and humans, identifies research gaps, and suggests directions for future research. Cases of disease in cats, dogs, and other domestic animals, often occurring through close contact with infected owners, are reviewed, raising concerns about possible zoonotic and reverse zoonotic transmission. Precautions and recommendations for pet owners and healthcare workers are also discussed. The scientific evidence presented in the article highlights the need for a One Health approach that considers the health of people, animals, and the environment to combat future pandemics. Full article

(This article belongs to the Special Issue Advanced Strategies against SARS-CoV-2 Variants and Future Emerging Virus Outbreaks)

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22 pages, 4569 KiB

Open AccessArticle

Spontaneous Lethal Outbreak of Influenza A Virus Infection in Vaccinated Sows on Two Farms Suggesting the Occurrence of Vaccine-Associated Enhanced Respiratory Disease with Eosinophilic Lung Pathology

by Wencke Reineking, Isabel Hennig-Pauka, Ludger Schröder, Ulf Höner, Elena Schreiber, Lukas Geiping, Simon Lassnig, Marta C. Bonilla, Marion Hewicker-Trautwein and Nicole de Buhr

Viruses 2024, 16(6), 955; https://doi.org/10.3390/v16060955 - 13 Jun 2024

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Abstract

Influenza A virus (IAV) infections in swine are usually subclinical, but they can reach high morbidity rates. The mortality rate is normally low. In this study, six vaccinated, spontaneously deceased sows revealed IAV infection and enhanced neutrophilic bronchopneumonia with unexpectedly large numbers of [...] Read more.

Influenza A virus (IAV) infections in swine are usually subclinical, but they can reach high morbidity rates. The mortality rate is normally low. In this study, six vaccinated, spontaneously deceased sows revealed IAV infection and enhanced neutrophilic bronchopneumonia with unexpectedly large numbers of infiltrating eosinophils. The purpose of this study was to characterize these lung lesions with special emphasis on the phenotypes of inflammatory cells, the presence of eosinophilic peroxidase (EPO), and neutrophil extracellular traps (NETs). The number of Sirius red-stained eosinophils was significantly higher in the lungs of IAV-infected sows compared to healthy pigs, indicating a migration of eosinophils from blood vessels into the lung tissue stimulated by IAV infection. The detection of intra- and extracellular EPO in the lungs suggests its contribution to pulmonary damage. The presence of CD3⁺ T lymphocytes, CD20⁺ B lymphocytes, and Iba-1⁺ macrophages indicates the involvement of cell-mediated immune responses in disease progression. Furthermore, high numbers of myeloperoxidase-positive cells were detected. However, DNA-histone-1 complexes were reduced in IAV-infected sows, leading to the hypothesis that NETs are not formed in the IAV-infected sows. In conclusion, our findings in the lungs of IAV-infected vaccinated sows suggest the presence of so far unreported field cases of vaccine-associated enhanced respiratory disease. Full article

(This article belongs to the Special Issue Advances in Animal Influenza Virus Research: Third Edition)

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10 pages, 1564 KiB

Open AccessArticle

Hepatitis B Virus Genotypes and Subgenotypes Circulating in Infected Residents in a Country with High Vaccination Rate

by Carolina Silva, Diogo Ramos, Miriam Quina and Elizabeth Pádua

Viruses 2024, 16(6), 954; https://doi.org/10.3390/v16060954 - 13 Jun 2024

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Abstract

Despite the availability of a vaccine against hepatitis B virus (HBV), this infection still causes public health problems, particularly in susceptible populations. In Portugal, universal free vaccination started in 1994, and most HBV infections are diagnosed in immigrants from high-prevalence countries. Our aim [...] Read more.

Despite the availability of a vaccine against hepatitis B virus (HBV), this infection still causes public health problems, particularly in susceptible populations. In Portugal, universal free vaccination started in 1994, and most HBV infections are diagnosed in immigrants from high-prevalence countries. Our aim was to assess the pattern of HBV genotypes/subgenotypes in samples collected between 2017 and 2021 from a convenience sample of 70 infected residents in Portugal. The HBV pol/HBsAg region was amplified and sequenced, allowing the analysis of RT sequences submitted to phylogenetic analysis and mutations assessment. A total of 37.1% of samples were from native Portuguese, aged 25–53 years (mean: 36.7 years), and the remaining samples were from individuals born outside of Portugal. A high diversity of HBV was identified: subgenotypes A1–A3 in 41.0% (16/39); D1, D3, and D4 in 30.7% (12/39); E in 23.1% (9/39); and F4 in 2.6% (1/39). Besides genotypes A and D, Portuguese were also infected with genotypes E and F, which are prevalent in Africa and South America, respectively. Resistance mutations in RT sequences were not found. The findings provide valuable insights for updating the HBV molecular epidemiology in Portugal. However, successful strategies to prevent and control the infection are still needed in the country, especially among susceptible and vulnerable populations. Full article

(This article belongs to the Special Issue Elimination of Viral Hepatitis: Improving Diagnosis, Treatment and Surveillance 2.0)

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19 pages, 4389 KiB

Open AccessArticle

Exploring the Complexity of the Human Respiratory Virome through an In Silico Analysis of Shotgun Metagenomic Data Retrieved from Public Repositories

by Talya Conradie, Jose A. Caparros-Martin, Siobhon Egan, Anthony Kicic, Sulev Koks, Stephen M. Stick and Patricia Agudelo-Romero

Viruses 2024, 16(6), 953; https://doi.org/10.3390/v16060953 - 13 Jun 2024

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Abstract

Background: Respiratory viruses significantly impact global morbidity and mortality, causing more disease in humans than any other infectious agent. Beyond pathogens, various viruses and bacteria colonize the respiratory tract without causing disease, potentially influencing respiratory diseases’ pathogenesis. Nevertheless, our understanding of respiratory microbiota [...] Read more.

Background: Respiratory viruses significantly impact global morbidity and mortality, causing more disease in humans than any other infectious agent. Beyond pathogens, various viruses and bacteria colonize the respiratory tract without causing disease, potentially influencing respiratory diseases’ pathogenesis. Nevertheless, our understanding of respiratory microbiota is limited by technical constraints, predominantly focusing on bacteria and neglecting crucial populations like viruses. Despite recent efforts to improve our understanding of viral diversity in the human body, our knowledge of viral diversity associated with the human respiratory tract remains limited. Methods: Following a comprehensive search in bibliographic and sequencing data repositories using keyword terms, we retrieved shotgun metagenomic data from public repositories (n = 85). After manual curation, sequencing data files from 43 studies were analyzed using EVEREST (pipEline for Viral assEmbly and chaRactEriSaTion). Complete and high-quality contigs were further assessed for genomic and taxonomic characterization. Results: Viral contigs were obtained from 194 out of the 868 FASTQ files processed through EVEREST. Of the 1842 contigs that were quality assessed, 8% (n = 146) were classified as complete/high-quality genomes. Most of the identified viral contigs were taxonomically classified as bacteriophages, with taxonomic resolution ranging from the superkingdom level down to the species level. Captured contigs were spread across 25 putative families and varied between RNA and DNA viruses, including previously uncharacterized viral genomes. Of note, airway samples also contained virus(es) characteristic of the human gastrointestinal tract, which have not been previously described as part of the lung virome. Additionally, by performing a meta-analysis of the integrated datasets, ecological trends within viral populations linked to human disease states and their biogeographical distribution along the respiratory tract were observed. Conclusion: By leveraging publicly available repositories of shotgun metagenomic data, the present study provides new insights into viral genomes associated with specimens from the human respiratory tract across different disease spectra. Further studies are required to validate our findings and evaluate the potential impact of these viral communities on respiratory tract physiology. Full article

(This article belongs to the Special Issue Virus Bioinformatics 2024)

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12 pages, 1608 KiB

Open AccessArticle

Development and Validation of an Enzyme-Linked Immunosorbent Assay-Based Protocol for Evaluation of Respiratory Syncytial Virus Vaccines

by Eliel Nham, A-Yeung Jang, Hyun Jung Ji, Ki Bum Ahn, Joon-Yong Bae, Man-Seong Park, Jin Gu Yoon, Hye Seong, Ji Yun Noh, Hee Jin Cheong, Woo Joo Kim, Ho Seong Seo and Joon Young Song

Viruses 2024, 16(6), 952; https://doi.org/10.3390/v16060952 - 12 Jun 2024

Viewed by 399

Abstract

Recently, respiratory syncytial virus (RSV) vaccines based on the prefusion F (pre-F) antigen were approved in the United States. We aimed to develop an enzyme-linked immunosorbent assay (ELISA)-based protocol for the practical and large-scale evaluation of RSV vaccines. Two modified pre-F proteins (DS-Cav1 [...] Read more.

Recently, respiratory syncytial virus (RSV) vaccines based on the prefusion F (pre-F) antigen were approved in the United States. We aimed to develop an enzyme-linked immunosorbent assay (ELISA)-based protocol for the practical and large-scale evaluation of RSV vaccines. Two modified pre-F proteins (DS-Cav1 and SC-TM) were produced by genetic recombination and replication using an adenoviral vector. The protocol was established by optimizing the concentrations of the coating antigen (pre-F proteins), secondary antibodies, and blocking buffer. To validate the protocol, we examined its accuracy, precision, and specificity using serum samples from 150 participants across various age groups and the standard serum provided by the National Institute of Health. In the linear correlation analysis, coating concentrations of 5 and 2.5 μg/mL of DS-Cav1 and SC-TM showed high coefficients of determination (r > 0.90), respectively. Concentrations of secondary antibodies (alkaline phosphatase-conjugated anti-human immunoglobulin G, diluted 1:2000) and blocking reagents (5% skim milk/PBS-T) were optimized to minimize non-specific reactions. High accuracy was observed for DS-Cav1 (r = 0.90) and SC-TM (r = 0.86). Further, both antigens showed high precision (coefficient of variation < 15%). Inhibition ELISA revealed cross-reactivity of antibodies against DS-Cav1 and SC-TM, but not with the attachment (G) protein. Full article

(This article belongs to the Special Issue Influenza, SARS-CoV-2, RSV and Other Vaccines: Immunogenicity Parameters and Protection, 3rd Edition)

19 pages, 1527 KiB

Open AccessReview

Breakthrough Acute HIV Infections among Pre-Exposure Prophylaxis Users with High Adherence: A Narrative Review

by Davide Moschese, Samuel Lazzarin, Martina Laura Colombo, Francesco Caruso, Andrea Giacomelli, Spinello Antinori and Andrea Gori

Viruses 2024, 16(6), 951; https://doi.org/10.3390/v16060951 - 12 Jun 2024

Viewed by 357

Abstract

Pre-exposure prophylaxis (PrEP) is a pivotal intervention among HIV prevention strategies. We aimed to narratively revise the topic of HIV acute infection in the setting of PrEP exposure with a focus on diagnostic options, clinical features, and future PrEP perspectives, with a particular [...] Read more.

Pre-exposure prophylaxis (PrEP) is a pivotal intervention among HIV prevention strategies. We aimed to narratively revise the topic of HIV acute infection in the setting of PrEP exposure with a focus on diagnostic options, clinical features, and future PrEP perspectives, with a particular focus on users with high adherence to PrEP. We searched the main databases (PubMed, Embase, and Scopus) with the keywords “PrEP” or “Pre-Exposure Prophylaxis” and “HIV” or “PLWH” and “breakthrough” or “acute infection” or “primary infection”. We included all randomized clinical trials and non-experimental studies (both case reports and observational studies) ever published. In the present narrative review, we revise the diagnostic challenges related to HIV diagnosis in the setting of PrEP and the clinical characteristics and symptoms of breakthrough infections. We discuss the management of acute HIV infection during PrEP and the new challenges that arise from the use of long-acting drugs for PrEP. Our review underlines that although extremely rare, HIV seroconversions are still possible during PrEP, even in a context of high adherence. Efforts to promptly identify these events must be included in the PrEP follow-up in order to minimize the chance of overlooked HIV breakthrough infections and thus exposure to suboptimal concentrations of antiretrovirals. Full article

(This article belongs to the Special Issue Acute HIV Infections)

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19 pages, 604 KiB

Open AccessArticle

Inflammatory and Autoimmune Aspects of Multisystem Inflammatory Syndrome in Children (MIS-C): A Prospective Cohort Study

by David A. Lawrence, Aishwarya Jadhav, Tapan K. Mondal, Kyle Carson, William T. Lee, Alexander H. Hogan, Katherine W. Herbst, Ian C. Michelow, Michael Brimacombe, Juan C. Salazar and The Connecticut Children’s COVID Collaborative

Viruses 2024, 16(6), 950; https://doi.org/10.3390/v16060950 - 12 Jun 2024

Viewed by 357

Abstract

Multisystem Inflammatory Syndrome in Children (MIS-C) is a potentially life-threatening complication of COVID-19. The pathophysiological mechanisms leading to severe disease are poorly understood. This study leveraged clinical samples from a well-characterized cohort of children hospitalized with COVID-19 or MIS-C to compare immune-mediated biomarkers. [...] Read more.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a potentially life-threatening complication of COVID-19. The pathophysiological mechanisms leading to severe disease are poorly understood. This study leveraged clinical samples from a well-characterized cohort of children hospitalized with COVID-19 or MIS-C to compare immune-mediated biomarkers. Our objective was to identify selected immune molecules that could explain, in part, why certain SARS-CoV-2-infected children developed MIS-C. We hypothesized that type-2 helper T cell-mediated inflammation can elicit autoantibodies, which may account for some of the differences observed between the moderate–severe COVID-19 (COVID⁺) and MIS-C cohort. We enumerated blood leukocytes and measured levels of selected serum cytokines, chemokines, antibodies to COVID-19 antigens, and autoantibodies in children presenting to an academic medical center in Connecticut, United States. The neutrophil/lymphocyte and eosinophil/lymphocyte ratios were significantly higher in those in the MIS-C versus COVID⁺ cohort. IgM and IgA, but not IgG antibodies to SARS-CoV-2 receptor binding domain were significantly higher in the MIS-C cohort than the COVID⁺ cohort. The serum levels of certain type-2 cytokines (interleukin (IL)-4, IL-5, IL-6, IL-8, IL-10, IL-13, and IL-33) were significantly higher in children with MIS-C compared to the COVID⁺ and SARS-CoV-2-negative cohorts. IgG autoantibodies to brain antigens and pentraxin were higher in children with MIS-C compared to SARS-CoV-19-negative controls, and children with MIS-C had higher levels of IgG anti-contactin-associated protein-like 2 (caspr2) compared to the COVID⁺ and SARS-CoV-19-negative controls. We speculate that autoimmune responses in certain COVID-19 patients may induce pathophysiological changes that lead to MIS-C. The triggers of autoimmunity and factors accounting for type-2 inflammation require further investigation. Full article

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

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10 pages, 3158 KiB

Open AccessArticle

The MGF300-2R Protein of African Swine Fever Virus Promotes IKKβ Ubiquitination by Recruiting the E3 Ubiquitin Ligase TRIM21

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

Viruses 2024, 16(6), 949; https://doi.org/10.3390/v16060949 - 12 Jun 2024

Viewed by 327

Abstract

African swine fever (ASF) is an acute, hemorrhagic, highly contagious disease in pigs caused by African swine fever virus (ASFV). Our previous study identified that the ASFV MGF300-2R protein functions as a virulence factor and found that MGF300-2R degrades IKKβ via selective [...] Read more.

African swine fever (ASF) is an acute, hemorrhagic, highly contagious disease in pigs caused by African swine fever virus (ASFV). Our previous study identified that the ASFV MGF300-2R protein functions as a virulence factor and found that MGF300-2R degrades IKKβ via selective autophagy. However, the E3 ubiquitin ligase responsible for IKKβ ubiquitination during autophagic degradation still remains unknown. In order to solve this problem, we first pulled down 328 proteins interacting with MGF300-2R through immunoprecipitation-mass spectrometry. Next, we analyzed and confirmed the interaction between the E3 ubiquitin ligase TRIM21 and MGF300-2R and demonstrated the catalytic role of TRIM21 in IKKβ ubiquitination. Finally, we indicated that the degradation of IKKβ by MGF300-2R was dependent on TRIM21. In summary, our results indicate TRIM21 is the E3 ubiquitin ligase involved in the degradation of IKKβ by MGF300-2R, thereby augmenting our understanding of the functions of MGF300-2R and offering insights into the rational design of live attenuated vaccines and antiviral strategies against ASF. Full article

(This article belongs to the Special Issue African Swine Fever Virus 4.0)

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13 pages, 1215 KiB

Open AccessArticle

Antiviral Activities of Mastoparan-L-Derived Peptides against Human Alphaherpesvirus 1

by Liana Costa Pereira Vilas Boas, Danieli Fernanda Buccini, Rhayfa Lorrayne Araújo Berlanda, Bruno de Paula Oliveira Santos, Mariana Rocha Maximiano, Luciano Morais Lião, Sónia Gonçalves, Nuno C. Santos and Octávio Luiz Franco

Viruses 2024, 16(6), 948; https://doi.org/10.3390/v16060948 - 12 Jun 2024

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Abstract

Human alphaherpesvirus 1 (HSV-1) is a significantly widespread viral pathogen causing recurrent infections that are currently incurable despite available treatment protocols. Studies have highlighted the potential of antimicrobial peptides sourced from Vespula lewisii venom, particularly those belonging to the mastoparan family, as effective [...] Read more.

Human alphaherpesvirus 1 (HSV-1) is a significantly widespread viral pathogen causing recurrent infections that are currently incurable despite available treatment protocols. Studies have highlighted the potential of antimicrobial peptides sourced from Vespula lewisii venom, particularly those belonging to the mastoparan family, as effective against HSV-1. This study aimed to demonstrate the antiviral properties of mastoparans, including mastoparan-L [I⁵, R⁸], mastoparan-MO, and [I⁵, R⁸] mastoparan, against HSV-1. Initially, Vero cell viability was assessed in the presence of these peptides, followed by the determination of antiviral activity, mechanism of action, and dose-response curves through plaque assays. Structural analyses via circular dichroism and nuclear magnetic resonance were conducted, along with evaluating membrane fluidity changes induced by [I⁵, R⁸] mastoparan using fluorescence-labeled lipid vesicles. Cytotoxic assays revealed high cell viability (>80%) at concentrations of 200 µg/mL for mastoparan-L and mastoparan-MO and 50 µg/mL for [I⁵, R⁸] mastoparan. Mastoparan-MO and [I⁵, R⁸] mastoparan exhibited over 80% HSV-1 inhibition, with up to 99% viral replication inhibition, particularly in the early infection stages. Structural analysis indicated an α-helical structure for [I⁵, R⁸] mastoparan, suggesting effective viral particle disruption before cell attachment. Mastoparans present promising prospects for HSV-1 infection control, although further investigation into their mechanisms is warranted. Full article

(This article belongs to the Special Issue Antiviral Peptide)

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10 pages, 251 KiB

Open AccessArticle

Is Antiviral Treatment with Remdesivir at the Acute Phase of SARS-CoV-2 Infection Effective for Decreasing the Risk of Long-Lasting Post-COVID Symptoms?

by César Fernández-de-las-Peñas, Anabel Franco-Moreno, María Ruiz-Ruigómez, Estibaliz Arrieta-Ortubay, Pablo Ryan-Murua, Carlos Lumbreras-Bermejo, Pablo del-Valle-Loarte, Oscar J. Pellicer-Valero, Rocco Giordano, Lars Arendt-Nielsen, Isabel Martín-Garrido and Juan Torres-Macho

Viruses 2024, 16(6), 947; https://doi.org/10.3390/v16060947 - 12 Jun 2024

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Abstract

The aim of this study was to investigate the effects of administrating Remdesivir at the acute COVID-19 phase on developing post-COVID symptoms in previously hospitalized COVID-19 survivors by controlling factors such as age, sex, body mass index, and vaccination status. A case-control study [...] Read more.

The aim of this study was to investigate the effects of administrating Remdesivir at the acute COVID-19 phase on developing post-COVID symptoms in previously hospitalized COVID-19 survivors by controlling factors such as age, sex, body mass index, and vaccination status. A case-control study was performed. Hospitalized COVID-19 survivors who had received intravenous Remdesivir during the acute phase (n = 216) were matched by age, sex, body mass index, and vaccination status with survivors who did not receive antiviral treatment (n = 216). Participants were asked to self-report the presence of any post-COVID symptom (defined as a symptom that started no later than three months after infection) and whether the symptom persisted at the time of study (mean: 18.4, SD: 0.8 months). Anxiety levels (HADS-A), depressive symptoms (HADS-D), sleep quality (PSQI), and severity/disability (FIC) were also compared. The multivariate analysis revealed that administration of Remdesivir at the acute COVID-19 phase was a protective factor for long-term COVID development (OR0.401, 95%CI 0.256–0.628) and specifically for the following post-COVID symptoms: fatigue (OR0.399, 95%CI 0.270–0.590), pain (OR0.368, 95% CI 0.248–0.548), dyspnea at rest (OR0.580, 95%CI 0.361–0.933), concentration loss (OR0.368, 95%CI 0.151–0.901), memory loss (OR0.399, 95%CI 0.270–0.590), hair loss (OR0.103, 95%CI 0.052–0.207), and skin rashes (OR0.037, 95%CI 0.005–0.278). This study supports the potential protective role of intravenous administration of Remdesivir during the COVID-19 acute phase for long-lasting post-COVID symptoms in previously hospitalized COVID-19 survivors. Full article

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

8 pages, 624 KiB

Open AccessArticle

Clinical Characteristics and Outcomes of Pediatric COVID-19 Pneumonia Treated with Favipiravir in a Tertiary Care Center

by Phanthila Sitthikarnkha, Rawisara Phunyaissaraporn, Sirapoom Niamsanit, Leelawadee Techasatian, Suchaorn Saengnipanthkul and Rattapon Uppala

Viruses 2024, 16(6), 946; https://doi.org/10.3390/v16060946 - 12 Jun 2024

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Abstract

The COVID-19 pandemic, caused by SARS-CoV-2, has posed significant health challenges worldwide. While children generally experience less severe illness compared to adults, pneumonia remains a substantial risk, particularly for those under five years old. This study examines the clinical characteristics and treatment outcomes [...] Read more.

The COVID-19 pandemic, caused by SARS-CoV-2, has posed significant health challenges worldwide. While children generally experience less severe illness compared to adults, pneumonia remains a substantial risk, particularly for those under five years old. This study examines the clinical characteristics and treatment outcomes of pediatric COVID-19 pneumonia patients treated with favipiravir in Thailand, aiming to identify associated factors for pneumonia. A retrospective review was performed on pediatric patients aged 1 month to 18 years hospitalized with COVID-19 at Srinagarind Hospital, Khon Kaen University, from 13 January 2020 to 15 November 2021. Data on demographics, clinical symptoms, treatment, and outcomes were collected, and logistic regression analysis was used to identify factors associated with pneumonia. Among 349 hospitalized children, the median age was 8 years, with 51.9% being male. Symptoms included a fever (100%), a cough (74.2%), and a rash (24.9%). COVID-19 pneumonia was diagnosed in 54.7% of the children. Favipiravir was administered as the standard treatment, showing mild adverse effects, including a rash (4.3%) and nausea (2.8%). Monocytosis was significantly associated with COVID-19 pneumonia (aOR 30.85, 95% CI: 9.03–105.41, p < 0.001), with an ROC curve area of 0.77 (95% CI: 0.71–0.83). Pediatric COVID-19 patients typically exhibit mild-to-moderate symptoms, with pneumonia being common in the early pandemic phase. Monocytosis is a significant factor associated with COVID-19 pneumonia. Favipiravir demonstrated mild adverse effects. Further studies are needed to validate these findings across different settings and phases of the pandemic. Full article

(This article belongs to the Section Coronaviruses)

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16 pages, 2174 KiB

Open AccessArticle

Elucidation of the Epitranscriptomic RNA Modification Landscape of Chikungunya Virus

by Belinda Baquero-Pérez, Enrico Bortoletto, Umberto Rosani, Anna Delgado-Tejedor, Rebeca Medina, Eva Maria Novoa, Paola Venier and Juana Díez

Viruses 2024, 16(6), 945; https://doi.org/10.3390/v16060945 - 12 Jun 2024

Viewed by 420

Abstract

The genomes of positive-sense (+) single-stranded RNA (ssRNA) viruses are believed to be subjected to a wide range of RNA modifications. In this study, we focused on the chikungunya virus (CHIKV) as a model (+) ssRNA virus to study the landscape of viral [...] Read more.

The genomes of positive-sense (+) single-stranded RNA (ssRNA) viruses are believed to be subjected to a wide range of RNA modifications. In this study, we focused on the chikungunya virus (CHIKV) as a model (+) ssRNA virus to study the landscape of viral RNA modification in infected human cells. Among the 32 distinct RNA modifications analysed by mass spectrometry, inosine was found enriched in the genomic CHIKV RNA. However, orthogonal validation by Illumina RNA-seq analyses did not identify any inosine modification along the CHIKV RNA genome. Moreover, CHIKV infection did not alter the expression of ADAR1 isoforms, the enzymes that catalyse the adenosine to inosine conversion. Together, this study highlights the importance of a multidisciplinary approach to assess the presence of RNA modifications in viral RNA genomes. Full article

(This article belongs to the Special Issue Advances in Alphavirus and Flavivirus Research, 2nd Edition)

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8 pages, 2841 KiB

Open AccessBrief Report

Enhanced Recombinant Protein Expression in Insect Cells by Natural and Recombinant Components of Lepidoptera Hemolymph

by Javier López-Vidal, Susana Martínez-Pulgarín, Diego Martínez-Alonso, Miguel Cid and José M. Escribano

Viruses 2024, 16(6), 944; https://doi.org/10.3390/v16060944 - 12 Jun 2024

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Abstract

Prior research has established the anti-apoptotic effects in insect cell cultures of Bombyx mori (B. mori) hemolymph, as well as the heightened production yields of recombinant proteins facilitated by baculovirus vectors in insect cells cultivated in media supplemented with this hemolymph. [...] Read more.

Prior research has established the anti-apoptotic effects in insect cell cultures of Bombyx mori (B. mori) hemolymph, as well as the heightened production yields of recombinant proteins facilitated by baculovirus vectors in insect cells cultivated in media supplemented with this hemolymph. In this study, we investigated the hemolymph of another Lepidoptera species, Trichoplusia ni (T. ni), and observed similar beneficial effects in insect cells cultivated in media supplemented with this natural substance. We observed enhancements in both production yield (approximately 1.5 times higher) and late-stage cell viabilities post-infection (30–40% higher). Storage-protein 2 from B. mori (SP2Bm) has previously been identified as one of the abundant hemolymph proteins potentially responsible for the beneficial effects observed after the use of B. mori hemolymph-supplemented cell culture media. By employing a dual baculovirus vector that co-expresses the SP2Bm protein alongside the GFP protein, we achieved a threefold increase in reporter protein production compared to a baculovirus vector expressing GFP alone. This study underscores the potential of hemolymph proteins sourced from various Lepidoptera species as biotechnological tools to augment baculovirus vector productivities, whether utilized as natural supplements in cell culture media or as hemolymph-derived recombinant proteins co-expressed by baculovirus vectors. Full article

(This article belongs to the Special Issue The Application of Viruses to Biotechnology 3.0)

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