Journal Description
Viruses
Viruses
is a peer-reviewed, open access journal of virology, published monthly online by MDPI. The American Society for Virology (ASV), Spanish Society for Virology (SEV), Canadian Society for Virology (CSV), Italian Society for Virology (SIV-ISV), Australasian Virology Society (AVS) and others are affiliated with Viruses and their members receive a discount on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, MEDLINE, PMC, Embase, PubAg, AGRIS, and other databases.
- Journal Rank: JCR - Q2 (Virology) / CiteScore - Q1 (Infectious Diseases)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 16.1 days after submission; acceptance to publication is undertaken in 2.6 days (median values for papers published in this journal in the first half of 2024).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Companion journal: Zoonotic Diseases.
Impact Factor:
3.8 (2023);
5-Year Impact Factor:
4.0 (2023)
Latest Articles
Impact of SARS-CoV-2 on Viral Respiratory Infections in Patients with Hematological Malignancies
Viruses 2024, 16(10), 1520; https://doi.org/10.3390/v16101520 (registering DOI) - 26 Sep 2024
Abstract
Patients with hematological malignancies (HMs) are at high risk of respiratory viral infections due to the intrinsic deterioration of the immune system and chemotherapy treatments. In the recent past, SARS-CoV-2 respiratory viral infection has been responsible for most infectious complications in HMs. We
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Patients with hematological malignancies (HMs) are at high risk of respiratory viral infections due to the intrinsic deterioration of the immune system and chemotherapy treatments. In the recent past, SARS-CoV-2 respiratory viral infection has been responsible for most infectious complications in HMs. We analyzed 2950 samples from 505 patients admitted to the Hematology department from 2019 to 2023. The aim of this study was to determine the epidemiological trend of respiratory viruses in the SARS-CoV-2 era, the characteristics of the patients involved and their outcomes. In our analysis, we found a reduction in non-SARS-CoV-2 respiratory viral (NSRV) positivity during the pandemic period, although these data did not show statistical significance. Most of the HMs involved were Multiple Myeloma and Acute Myeloid Leukemia. Overall mortality rate was very low and characterized by the progression of the HMs as well as the worsening of respiratory failure. In conclusion, a reduction in non-COVID viral infections was highlighted, probably also thanks to the increase in prevention measures and environmental modifications of the viral background.
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(This article belongs to the Section Coronaviruses)
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Pediatric Respiratory Hospitalizations in the Pre-COVID-19 Era: The Contribution of Viral Pathogens and Comorbidities to Clinical Outcomes, Valencia, Spain
by
Valérie Bosch Castells, Ainara Mira-Iglesias, Francisco Xavier López-Labrador, Beatriz Mengual-Chuliá, Mario Carballido-Fernández, Miguel Tortajada-Girbés, Joan Mollar-Maseres, Joan Puig-Barberà, Javier Díez-Domingo and Sandra S. Chaves
Viruses 2024, 16(10), 1519; https://doi.org/10.3390/v16101519 (registering DOI) - 25 Sep 2024
Abstract
Viral respiratory diseases place a heavy burden on the healthcare system, with children making up a significant portion of related hospitalizations. While comorbidities increase the risk of complications and poor outcomes, many hospitalized children lack clear risk factors. As new vaccines for respiratory
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Viral respiratory diseases place a heavy burden on the healthcare system, with children making up a significant portion of related hospitalizations. While comorbidities increase the risk of complications and poor outcomes, many hospitalized children lack clear risk factors. As new vaccines for respiratory viral diseases emerge, this study examined pediatric respiratory hospitalizations, focusing on viral etiology, complication rates, and the impact of comorbidities to guide future policy. Data were analyzed from eight pre-COVID influenza seasons (2011/2012–2018/2019) involving patients under 18 years hospitalized with respiratory complaints across 4–10 hospitals in Valencia, Spain. Respiratory specimens were tested for eight viral targets using multiplex real-time reverse-transcription polymerase chain reaction. Demographics, clinical outcomes, discharge diagnoses, and laboratory results were examined. Among the hospitalized children, 26% had at least one comorbidity. These children had higher rates of pneumonia, asthma exacerbation, and pneumothorax, and were twice as likely to require ICU admission, though mechanical ventilation and length of stay were similar to those without comorbidities. Respiratory syncytial virus (RSV) was the most common virus detected (23.1%), followed by rhinovirus/enterovirus (9.5%) and influenza (7.2%). Viral codetection decreased with age, occurring in 4.6% of cases. Comorbidities increase the risk of complications in pediatric respiratory illnesses, however, healthcare utilization is driven largely by otherwise healthy children. Pediatric viral vaccines could reduce this burden and should be further evaluated.
Full article
(This article belongs to the Special Issue Influenza and Other Respiratory Viruses: Prevention, Diagnosis, Treatment)
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Open AccessArticle
Long Terminal Repeats of Gammaretroviruses Retain Stable Expression after Integration Retargeting
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Dalibor Miklík, Martina Slavková, Dana Kučerová, Chahrazed Mekadim, Jakub Mrázek and Jiří Hejnar
Viruses 2024, 16(10), 1518; https://doi.org/10.3390/v16101518 (registering DOI) - 25 Sep 2024
Abstract
Retroviruses integrate into the genomes of infected host cells to form proviruses, a genetic platform for stable viral gene expression. Epigenetic silencing can, however, hamper proviral transcriptional activity. As gammaretroviruses (γRVs) preferentially integrate into active promoter and enhancer sites, the high transcriptional activity
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Retroviruses integrate into the genomes of infected host cells to form proviruses, a genetic platform for stable viral gene expression. Epigenetic silencing can, however, hamper proviral transcriptional activity. As gammaretroviruses (γRVs) preferentially integrate into active promoter and enhancer sites, the high transcriptional activity of γRVs can be attributed to this integration preference. In addition, long terminal repeats (LTRs) of some γRVs were shown to act as potent promoters by themselves. Here, we investigate the capacity of different γRV LTRs to drive stable expression within a non-preferred epigenomic environment in the context of diverse retroviral vectors. We demonstrate that different γRV LTRs are either rapidly silenced or remain active for long periods of time with a predominantly active proviral population under normal and retargeted integration. As an alternative to the established γRV systems, the feline leukemia virus and koala retrovirus LTRs are able to drive stable, albeit intensity-diverse, transgene expression. Overall, we show that despite the occurrence of rapid silencing events, most γRV LTRs can drive stable expression outside of their preferred chromatin landscape after retrovirus integrations.
Full article
(This article belongs to the Section General Virology)
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Open AccessArticle
Kinetic Studies on the Interaction of HIV-1 Gag Protein with the HIV-1 RNA Packaging Signal
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Constance Rink, Tomas Kroupa, Siddhartha A. K. Datta and Alan Rein
Viruses 2024, 16(10), 1517; https://doi.org/10.3390/v16101517 - 25 Sep 2024
Abstract
During HIV-1 virus assembly, the genomic RNA (vRNA) is selected for packaging by the viral protein Gag because it contains a specific packaging signal, Psi. While there have been numerous studies of Gag–Psi interactions, there is almost no information on the kinetic aspects
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During HIV-1 virus assembly, the genomic RNA (vRNA) is selected for packaging by the viral protein Gag because it contains a specific packaging signal, Psi. While there have been numerous studies of Gag–Psi interactions, there is almost no information on the kinetic aspects of this interaction. We investigated the kinetics of Gag binding to different RNAs using switchSENSE DRX2 technology. We measured the association rate of Gag binding to monomeric Psi, to a “Multiple Binding Site Mutant” Psi that is inactive for genome packaging in vivo, and to a scrambled Psi. We discovered that Gag binds more rapidly to Psi RNA than to the mutant or scrambled RNAs. Furthermore, rapid Gag association kinetics are retained within sub-regions of Psi: Gag associates more rapidly with RNA containing only the 3′ two of the three Psi stem-loops than with monomeric RNA containing the 5′ two stem-loops or a scrambled RNA. No differences were detectable with individual Psi stem-loops. Interestingly, the rate of binding of Gag molecules to Psi increases with increasing Gag concentration, suggesting cooperativity in binding. The results are consistent with the hypothesis that selectivity in packaging derives from kinetic differences in initiation of particle assembly.
Full article
(This article belongs to the Special Issue 12th International Retroviral Symposium: Assembly, Maturation and Uncoating)
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Open AccessSystematic Review
Gastrointestinal Sequelae of COVID-19: Investigating Post-Infection Complications—A Systematic Review
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Ibrahim Mohammed, Sudharsan Podhala, Fariha Zamir, Shamha Shiyam, Abdel Rahman Salameh, Zoya Salahuddin, Huda Salameh, Chaehyun Kim, Zena Sinan, Jeongyeon Kim, Deema Al-Abdulla, Sa’ad Laws, Malik Mushannen and Dalia Zakaria
Viruses 2024, 16(10), 1516; https://doi.org/10.3390/v16101516 - 25 Sep 2024
Abstract
Gastrointestinal (GI) complications are significant manifestations of COVID-19 and are increasingly being recognized. These complications range from severe acute pancreatitis to colitis, adding complexity to diagnosis and management. A comprehensive database search was conducted using several databases. Our inclusion criteria encompassed studies reporting
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Gastrointestinal (GI) complications are significant manifestations of COVID-19 and are increasingly being recognized. These complications range from severe acute pancreatitis to colitis, adding complexity to diagnosis and management. A comprehensive database search was conducted using several databases. Our inclusion criteria encompassed studies reporting severe and long-term GI complications of COVID-19. Digestive disorders were categorized into infections, inflammatory conditions, vascular disorders, structural abnormalities, other diagnoses, and undiagnosed conditions. Of the 73 studies that were selected for full-text review, only 24 met our inclusion criteria. The study highlights a broad range of gastrointestinal complications following COVID-19 infection (excluding liver complications, which are examined separately), including inflammatory conditions, such as ulcerative colitis (UC), acute pancreatitis, and multisystem inflammatory syndrome in children (MIS-C). Other GI complications were reported such as vascular disorders, including diverse thrombotic events and structural abnormalities, which ranged from bowel perforations to adhesions. Additionally, undiagnosed conditions like nausea and abdominal pain were prevalent across different studies involving 561 patients. The findings emphasize the substantial impact of COVID-19 on the GI tract. Ongoing research and monitoring are crucial to understanding the long-term effects and developing effective management strategies for these complications.
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(This article belongs to the Special Issue COVID-19 Complications and Co-infections)
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Evolutionary Insights from Association Rule Mining of Co-Occurring Mutations in Influenza Hemagglutinin and Neuraminidase
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Valentina Galeone, Carol Lee, Michael T. Monaghan, Denis C. Bauer and Laurence O. W. Wilson
Viruses 2024, 16(10), 1515; https://doi.org/10.3390/v16101515 - 25 Sep 2024
Abstract
Seasonal influenza viruses continuously evolve via antigenic drift. This leads to recurring epidemics, globally significant mortality rates, and the need for annually updated vaccines. Co-occurring mutations in hemagglutinin (HA) and neuraminidase (NA) are suggested to have synergistic interactions where mutations can increase the
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Seasonal influenza viruses continuously evolve via antigenic drift. This leads to recurring epidemics, globally significant mortality rates, and the need for annually updated vaccines. Co-occurring mutations in hemagglutinin (HA) and neuraminidase (NA) are suggested to have synergistic interactions where mutations can increase the chances of immune escape and viral fitness. Association rule mining was used to identify temporal relationships of co-occurring HA–NA mutations of influenza virus A/H3N2 and its role in antigenic evolution. A total of 64 clusters were found. These included well-known mutations responsible for antigenic drift, as well as previously undiscovered groups. A majority (41/64) were associated with known antigenic sites, and 38/64 involved mutations across both HA and NA. The emergence and disappearance of N-glycosylation sites in the pattern of N-X-[S/T] were also identified, which are crucial post-translational processes to maintain protein stability and functional balance (e.g., emergence of NA:339ASP and disappearance of HA:187ASP). Our study offers an alternative approach to the existing mutual-information and phylogenetic methods used to identify co-occurring mutations, enabling faster processing of large amounts of data. Our approach can facilitate the prediction of critical mutations given their occurrence in a previous season, facilitating vaccine development for the next flu season and leading to better preparation for future pandemics.
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(This article belongs to the Special Issue Virus Bioinformatics 2024)
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Characterization of Nasal Mucosal T Cells in Horses and Their Response to Equine Herpesvirus Type 1
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Camille M. Holmes and Bettina Wagner
Viruses 2024, 16(10), 1514; https://doi.org/10.3390/v16101514 - 25 Sep 2024
Abstract
Equine herpesvirus type 1 (EHV-1) enters through the upper respiratory tract (URT). Mucosal immunity at the URT is crucial in limiting viral infection and morbidity. Here, intranasal immune cells were collected from horses (n = 15) during an experimental EHV-1 infection. CD4
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Equine herpesvirus type 1 (EHV-1) enters through the upper respiratory tract (URT). Mucosal immunity at the URT is crucial in limiting viral infection and morbidity. Here, intranasal immune cells were collected from horses (n = 15) during an experimental EHV-1 infection. CD4+ and CD8+ T cells were the major intranasal cell populations before infection and increased significantly by day six and fourteen post-infection, respectively. Nasal mucosal T cells were further characterized in healthy horses. Compared to peripheral blood mononuclear cells (PBMC), mucosal CD8+ T-cell percentages were elevated, while CD4+ T-cell percentages were similar. A small population of CD4+CD8+ T cells was also recovered from mucosal samples. Within the URT tissue, CD4+ cells predominantly accumulated in the epithelial layer, while most CD8+ cells resided deeper in the mucosa or the submucosa below the basement membrane. In vitro stimulation of mucosal cells from healthy horses with (n = 5) or without (n = 5) peripheral T-cell immunity against EHV-1 induced IFN-γ production in nasal T cells upon polyclonal stimulation. However, after EHV-1 re-stimulation, mucosal T cells failed to respond with IFN-γ. This work provided the first characterization of mucosal T-cell phenotypes and functions in the URT of healthy horses and during EHV-1 infection.
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(This article belongs to the Special Issue Animal Herpesvirus)
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Isolation, Identification and Genomic Analysis of Orange-Spotted Grouper Iridovirus Hainan Strain in China
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Helong Cao, Dongzhuo Zhang, Guanghui Mu, Siting Wu, Yurong Tu, Qiwei Qin and Jingguang Wei
Viruses 2024, 16(10), 1513; https://doi.org/10.3390/v16101513 - 24 Sep 2024
Abstract
The orange-spotted grouper (Epinephelus coioides) is an important mariculture fish in China. However, in recent years, with the rapid development of aquaculture activities, outbreaks of viral diseases have affected the grouper aquaculture industry, causing severe economic losses. In the present study,
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The orange-spotted grouper (Epinephelus coioides) is an important mariculture fish in China. However, in recent years, with the rapid development of aquaculture activities, outbreaks of viral diseases have affected the grouper aquaculture industry, causing severe economic losses. In the present study, we isolated and identified a virus from diseased, orange-spotted groupers from an aquaculture farm in Hainan Province, China. The isolated virus was identified as orange-spotted grouper iridovirus, hence named the orange-spotted grouper iridovirus Hainan strain (OSGIV-HN-2018-001). OSGIV-HN-2018-001 induces a cytopathic effect after the infection of mandarin fish (Siniperca chuatsi) brain clonal passage (SBC) cells. In addition, the cytoplasm of the OSGIV-HN-2018-001-infected SBC cells was found to contain a large number of hexagonal virus particles with a diameter of approximately 134 nm. Using the Illumina NovaSeq system, we assembled the sequence data and annotated the complete genome of OSGIV-HN-2018-001 (GenBank accession number: PP974677), which consisted of 110,699 bp and contained 122 open reading frames (ORFs). Phylogenetic tree analysis showed that OSGIV-HN-2018-001 was most closely related to ISKNV-ASB-23. The cumulative mortality rate of groupers infected with OSGIV-HN-2018-001 reached 100% on day 8. The spleens were enlarged and blackened after the dissection of the dying groupers. These results contribute to the understanding of the molecular regulatory mechanism of the iridovirus infection and provide a basis for iridovirus prevention.
Full article
(This article belongs to the Special Issue Iridoviruses, 2nd Edition)
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Methodological Validation and Inter-Laboratory Comparison of Microneutralization Assay for Detecting Anti-AAV9 Neutralizing Antibody in Human
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Shuangqing Yu, Qian Zhao, Cengceng Zhang, Diyi Fu, Xueyang Zhu, Jianfang Zhou, Wenhao Ma, Zheyue Dong, Xiaoliang Zhai, Lijie Jiang, Xiaohong Han, Shuyang Zhang, Xiaobing Wu and Xiaoyan Dong
Viruses 2024, 16(10), 1512; https://doi.org/10.3390/v16101512 - 24 Sep 2024
Abstract
Anti-AAV neutralizing Abs (NAbs) titer is usually measured by cell-based microneutralization (MN) assay and is crucial for patient screening in AAV-based gene therapy clinical trials. However, achieving uniform operation and comparable results among different laboratories remains challenging. Here, we established a standardized MN
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Anti-AAV neutralizing Abs (NAbs) titer is usually measured by cell-based microneutralization (MN) assay and is crucial for patient screening in AAV-based gene therapy clinical trials. However, achieving uniform operation and comparable results among different laboratories remains challenging. Here, we established a standardized MN assay for anti-AAV9 NAbs in human sera or plasma and transferred the method to the other two research teams. Then, we validated its parameters and tested a set of eight human samples in blind across all laboratories. The end-point titer, defined by a transduction inhibition of 50% (IC50), was calculated using curve-fit modelling. A mouse neutralizing monoclonal antibody in human negative serum was used for system quality control (QC), requiring inter-assay titer variation of <4-fold difference or geometric coefficient of variation (%GCV) of <50%. The assay demonstrated a sensitivity of 54 ng/mL and no cross-reactivity to 20 μg/mL anti-AAV8 MoAb. The intra-assay and inter-assay variation for the low positive QC were 7–35% and 22–41%, respectively. The titers of the blind samples showed excellent reproducibility within and among laboratories, with a %GCV of 18–59% and 23–46%, respectively. This study provides a commonly transferrable MN assay for evaluating anti-AAV9 NAbs in humans, supporting its application in clinical trials.
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(This article belongs to the Section Human Virology and Viral Diseases)
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Limited Short-Term Evolution of SARS-CoV-2 RNA-Dependent RNA Polymerase under Remdesivir Exposure in Upper Respiratory Compartments
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Vladimir Novitsky, Curt G. Beckwith, Kristin Carpenter-Azevedo, Jimin Shin, Joel Hague, Soya Sam, Jon Steingrimsson, Richard C. Huard, Kevin Lethbridge, Sujata Sahu, Kim Rapoza, Karen Chandran, Lauri Bazerman, Evelyn Hipolito, Isabella Diaz, Daniella Carnevale, August Guang, Fizza Gillani, Angela M. Caliendo and Rami Kantor
Viruses 2024, 16(10), 1511; https://doi.org/10.3390/v16101511 (registering DOI) - 24 Sep 2024
Abstract
Background: The extent of the SARS-CoV-2 short-term evolution under Remdesivir (RDV) exposure and whether it varies across different upper respiratory compartments are not fully understood. Methods: Patients hospitalized for COVID-19, with or without RDV therapy, were enrolled and completed up to three visits,
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Background: The extent of the SARS-CoV-2 short-term evolution under Remdesivir (RDV) exposure and whether it varies across different upper respiratory compartments are not fully understood. Methods: Patients hospitalized for COVID-19, with or without RDV therapy, were enrolled and completed up to three visits, in which they provided specimens from four respiratory compartments. Near full-length genome SARS-CoV-2 sequences were obtained from viral RNA, standard lineage and variant assignments were performed, and viral mutations in the RNA-dependent RNA polymerase (RdRp) region—the RDV target gene—were detected and compared between participants with and without RDV, across the four compartments, within participants across visits, and versus a larger sequence dataset. The statistical analysis used a generalized linear mixed-effects model. Results: A total of 139 sequences were obtained from 37 out of the 44 (84%) enrolled participants. The genotyping success varied across respiratory compartments, which ranged from 42% with oropharyngeal specimens to 67% with nasopharyngeal specimens and showed improvement with higher viral loads. No RdRp mutations known to be associated with RDV resistance were identified, and for 34 detected mutations at 32 amino acid positions that are not known as RDV-associated, there was no evidence of any associations with the RDV exposure, respiratory compartment, or time. At least 1 of these 34 mutations were detected in all participants, and some differed from the larger sequence dataset. Conclusions: This study highlighted the SARS-CoV-2 short-term genomic stability within hosts and across upper respiratory compartments, which suggests a lack of evolution of RDV resistance over time. This contributes to our understanding of SARS-CoV-2 genomic dynamics.
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(This article belongs to the Section Coronaviruses)
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Chlorine Dioxide: Antiviral That Reduces the Spread of ToBRFV in Tomato (Solanum lycopersicum L.) Plants
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Ubilfrido Vásquez Gutiérrez, Gustavo Alberto Frías Treviño, Juan Carlos Delgado Ortiz, Luis Alberto Aguirre Uribe, Alberto Flores Olivas, Mariana Beltrán Beache and Francisco Daniel Hernández Castillo
Viruses 2024, 16(10), 1510; https://doi.org/10.3390/v16101510 - 24 Sep 2024
Abstract
Tomato brown rugose fruit virus (ToBRFV), being a mechanically transmitted disease, is usually difficult to control; therefore, an effective alternative to reduce transmission and replication in the crop is by spraying with chlorine dioxide (ClO2) during routine crop management. In this
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Tomato brown rugose fruit virus (ToBRFV), being a mechanically transmitted disease, is usually difficult to control; therefore, an effective alternative to reduce transmission and replication in the crop is by spraying with chlorine dioxide (ClO2) during routine crop management. In this research, the efficacy of chlorine dioxide (ClO2) for ToBRFV management in a greenhouse and open field was determined. The phytotoxicity of ClO2 and its effective concentration against ToBRFV in Nicotiana longiflora plants were evaluated. Subsequently, the effect of ClO2 on ToBRFV was evaluated in tomato plants grown in an open field. Finally, the effectiveness of ClO2 on plants inoculated with ToBRFV under greenhouse conditions was evaluated and the number of necrotic local lesions (NLLs) was quantified. The results revealed that ClO2 at 760 mg L−1 did not show phytotoxicity and reduced the number of NLLs in N. longiflora plants. It also decreased ToBRFV transmission and replication in field- and greenhouse-grown tomato plants, improving agronomic parameters. ClO2 reduced replication in plants inoculated with different amounts of ToBRFV inoculum in a greenhouse. N. longiflora leaves expressed lower numbers of NLLs when inoculated with ClO2-treated tomato plant extracts. Finally, the results demonstrate that ClO2 represents an effective management alternative when used by direct application to plants. To our knowledge, this is the first study where the use of an antiviral compound is carried out under field and greenhouse conditions.
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(This article belongs to the Special Issue Plant Virus Interactions with Hosts: Mechanisms and Applications)
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Cannabis Use and Cannabidiol Modulate HIV-Induced Alterations in TREM2 Expression: Implications for Age-Related Neuropathogenesis
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Bryant Avalos, Jacqueline R. Kulbe, Mary K. Ford, Anna Elizabeth Laird, Kyle Walter, Michael Mante, Jazmin B. Florio, Ali Boustani, Antoine Chaillon, Johannes C. M. Schlachetzki, Erin E. Sundermann, David J. Volsky, Robert A. Rissman, Ronald J. Ellis, Scott L. Letendre, Jennifer Iudicello and Jerel Adam Fields
Viruses 2024, 16(10), 1509; https://doi.org/10.3390/v16101509 - 24 Sep 2024
Abstract
Triggering receptor expressed on myeloid cells 2 (TREM2) is involved in neuroinflammation and HIV-associated neurocognitive impairment (NCI). People with HIV (PWH) using cannabis exhibit lower inflammation and neurological disorders. We hypothesized that TREM2 dysfunction mediates HIV neuropathogenesis and can be reversed by cannabinoids.
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Triggering receptor expressed on myeloid cells 2 (TREM2) is involved in neuroinflammation and HIV-associated neurocognitive impairment (NCI). People with HIV (PWH) using cannabis exhibit lower inflammation and neurological disorders. We hypothesized that TREM2 dysfunction mediates HIV neuropathogenesis and can be reversed by cannabinoids. EcoHIV-infected wildtype (WT) and TREM2R47H mutant mice were used to study HIV’s impact on TREM2 and behavior. TREM2 and related gene expressions were examined in monocyte-derived macrophages (MDMs) from PWH (n = 42) and people without HIV (PWoH; n = 19) with varying cannabis use via RNA sequencing and qPCR. Differences in membrane-bound and soluble TREM2 (sTREM2) were evaluated using immunocytochemistry (ICC) and ELISA. EcoHIV increased immature and C-terminal fragment forms of TREM2 in WT mice but not in TREM2R47H mice, with increased IBA1 protein in TREM2R47H hippocampi, correlating with worse memory test performance. TREM2 mRNA levels increased with age in PWoH but not in PWH. Cannabidiol (CBD) treatment increased TREM2 mRNA alone and with IL1β. RNA-seq showed the upregulation of TREM2-related transcripts in cannabis-using PWH compared to naïve controls. IL1β increased sTREM2 and reduced membrane-bound TREM2, effects partially reversed by CBD. These findings suggest HIV affects TREM2 expression modulated by cannabis and CBD, offering insights for therapeutic strategies.
Full article
(This article belongs to the Special Issue HIV and Drugs of Abuse, 3rd Edition)
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Preclinical Profile of the HIV-1 Maturation Inhibitor VH3739937
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Brian McAuliffe, Paul Falk, Jie Chen, Yan Chen, Sing-Yuen Sit, Jacob Swidorski, Richard A. Hartz, Li Xu, Brian Venables, Ny Sin, Nicholas A. Meanwell, Alicia Regueiro-Ren, David Wensel, Umesh Hanumegowda and Mark Krystal
Viruses 2024, 16(10), 1508; https://doi.org/10.3390/v16101508 - 24 Sep 2024
Abstract
The HIV-1 maturation inhibitor (MI) VH3739937 (VH-937) inhibits cleavage between capsid and spacer peptide 1 and exhibits an oral half-life in humans compatible with once-weekly dosing. Here, the antiviral properties of VH-937 are described. VH-937 exhibited potent antiviral activity against all HIV-1 laboratory
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The HIV-1 maturation inhibitor (MI) VH3739937 (VH-937) inhibits cleavage between capsid and spacer peptide 1 and exhibits an oral half-life in humans compatible with once-weekly dosing. Here, the antiviral properties of VH-937 are described. VH-937 exhibited potent antiviral activity against all HIV-1 laboratory strains, clinical isolates, and recombinant viruses examined, with half-maximal effective concentration (EC50) values ≤ 5.0 nM. In multiple-cycle assays, viruses less susceptible to other MIs, including A364V, were inhibited at EC50 values ≤ 8.0 nM and maximal percent inhibition (MPI) values ≥ 92%. However, VH-937 was less potent against A364V in single-cycle assays (EC50, 32.0 nM; MPI, 57%) and A364V emerged in one of four resistance selection cultures. Other substitutions were selected by VH-937, although re-engineered viruses with these sequences were non-functional in multiple-cycle assays. Measured dissociation rates from wild-type and A364V-containing VLPs help explain resistance to the A364V mutation. Overall, the in vitro antiviral activity of VH-937 supports its continued development as a treatment for HIV-1.
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(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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Redundancy in Innate Immune Pathways That Promote CD8+ T-Cell Responses in AAV1 Muscle Gene Transfer
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Ning Li, Sandeep R. P. Kumar, Di Cao, Maite Munoz-Melero, Sreevani Arisa, Bridget A. Brian, Calista M. Greenwood, Kentaro Yamada, Dongsheng Duan and Roland W. Herzog
Viruses 2024, 16(10), 1507; https://doi.org/10.3390/v16101507 - 24 Sep 2024
Abstract
While adeno-associated viral (AAV) vectors are successfully used in a variety of in vivo gene therapy applications, they continue to be hampered by the immune system. Here, we sought to identify innate and cytokine signaling pathways that promote CD8+ T-cell responses against
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While adeno-associated viral (AAV) vectors are successfully used in a variety of in vivo gene therapy applications, they continue to be hampered by the immune system. Here, we sought to identify innate and cytokine signaling pathways that promote CD8+ T-cell responses against the transgene product upon AAV1 vector administration to murine skeletal muscle. Eliminating just one of several pathways (including DNA sensing via TLR9, IL-1 receptor signaling, and possibly endosomal sensing of double-stranded RNA) substantially reduced the CD8+ T-cell response at lower vector doses but was surprisingly ineffective at higher doses. Using genetic, antibody-mediated, and vector engineering approaches, we show that blockade of at least two innate pathways is required to achieve an effect at higher vector doses. Concurrent blockade of IL-1R1 > MyD88 and TLR9 > MyD88 > type I IFN > IFNaR pathways was often but not always synergistic and had limited utility in preventing antibody formation against the transgene product. Further, even low-frequency CD8+ T-cell responses could eliminate transgene expression, even in MyD88- or IL-1R1-deficient animals that received a low vector dose. However, we provide evidence that CpG depletion of vector genomes and including TLR9 inhibitory sequences can synergize. When this construct was combined with the use of a muscle-specific promoter, transgene expression in muscle was sustained with minimal local or systemic CD8+ T-cell response. Thus, innate immune avoidance/blockade strategies by themselves, albeit helpful, may not be sufficient to prevent destructive cellular responses in muscle gene transfer because of the redundancy of immune-activating pathways.
Full article
(This article belongs to the Special Issue Virology and Immunology of Gene Therapy)
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Putting a Kink in HIV-1 Particle Infectivity: Rocaglamide Inhibits HIV-1 Replication by Altering Gag-Genomic RNA Interaction
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Paul Rosenfeld, Gatikrushna Singh, Amanda Paz Herrera, Juan Ji, Bradley Seufzer, Xiao Heng, Kathleen Boris-Lawrie and Alan Cochrane
Viruses 2024, 16(9), 1506; https://doi.org/10.3390/v16091506 - 23 Sep 2024
Abstract
Our examination of RNA helicases for effects on HIV-1 protein production and particle assembly identified Rocaglamide (RocA), a known modulator of eIF4A1 function, as an inhibitor of HIV-1 replication in primary CD4+ T cells and three cell systems. HIV-1 attenuation by low-nM
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Our examination of RNA helicases for effects on HIV-1 protein production and particle assembly identified Rocaglamide (RocA), a known modulator of eIF4A1 function, as an inhibitor of HIV-1 replication in primary CD4+ T cells and three cell systems. HIV-1 attenuation by low-nM RocA doses was associated with reduced viral particle formation without a marked decrease in Gag production. Rather, the co-localization of Gag and HIV-1 genomic RNA (gRNA) assemblies was impaired by RocA treatment in a reversible fashion. Ribonucleoprotein (RNP) immunoprecipitation studies recapitulated the loss of Gag-gRNA assemblies upon RocA treatment. Parallel biophysical studies determined that neither RocA nor eIF4A1 independently affected the ability of Gag to interact with viral RNA, but together, they distorted the structure of the HIV-1 RNP visualized by electron microscopy. Taken together, several lines of evidence indicate that RocA induces stable binding of eIF4A1 onto the viral RNA genome in a manner that interferes with the ordered assembly of Gag along Gag-gRNA assemblies required to generate infectious virions.
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(This article belongs to the Special Issue HIV Assembly, Release and Maturation)
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Open AccessArticle
Clinical Evaluation of the VirClia IgM/IgG Chemiluminescence Tests for the Diagnosis of Tick-Borne Encephalitis in an Endemic Part of Norway
by
Åshild Marvik and Susanne Gjeruldsen Dudman
Viruses 2024, 16(9), 1505; https://doi.org/10.3390/v16091505 - 23 Sep 2024
Abstract
The aim of this study was to evaluate the clinical usefulness of VirClia IgM/IgG single-assay chemiluminescence tests for the diagnosis of tick-borne encephalitis (TBE) in an endemic part of Norway. Patients hospitalized at Vestfold or Telemark Hospitals with suspected infection in the central
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The aim of this study was to evaluate the clinical usefulness of VirClia IgM/IgG single-assay chemiluminescence tests for the diagnosis of tick-borne encephalitis (TBE) in an endemic part of Norway. Patients hospitalized at Vestfold or Telemark Hospitals with suspected infection in the central nervous system (CNS) in the period between May 2021 and December 2023 were included, with 85 TBE cases identified. The VirClia IgM assay was positive in the initial serum sample in 75/85 cases, giving a sensitivity of 88.2% (95% CI, 79.4–94.2). The ReaScan TBE IgM rapid test was positive in 80/85 cases, with an estimated sensitivity of 94.1% (95% CI, 86.8–98.1). Vaccine breakthrough infections were the predominant cause of non-reactive IgM cases. The calculated specificity for the VirClia IgM was 95.8% (95% CI, 92.5–98.0). In conclusion, the sensitivity of the VirClia IgM was non-inferior to the ReaScan TBE IgM rapid test. However, isolated IgM reactive results must be interpreted with caution, since false-reactive results occur.
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(This article belongs to the Special Issue Tick-Borne Viruses: Transmission and Surveillance)
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Open AccessReview
Zooming in and out: Exploring RNA Viral Infections with Multiscale Microscopic Methods
by
Cheng-An Lyu, Yao Shen and Peijun Zhang
Viruses 2024, 16(9), 1504; https://doi.org/10.3390/v16091504 - 23 Sep 2024
Abstract
RNA viruses, being submicroscopic organisms, have intriguing biological makeups and substantially impact human health. Microscopic methods have been utilized for studying RNA viruses at a variety of scales. In order of observation scale from large to small, fluorescence microscopy, cryo-soft X-ray tomography (cryo-SXT),
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RNA viruses, being submicroscopic organisms, have intriguing biological makeups and substantially impact human health. Microscopic methods have been utilized for studying RNA viruses at a variety of scales. In order of observation scale from large to small, fluorescence microscopy, cryo-soft X-ray tomography (cryo-SXT), serial cryo-focused ion beam/scanning electron microscopy (cryo-FIB/SEM) volume imaging, cryo-electron tomography (cryo-ET), and cryo-electron microscopy (cryo-EM) single-particle analysis (SPA) have been employed, enabling researchers to explore the intricate world of RNA viruses, their ultrastructure, dynamics, and interactions with host cells. These methods evolve to be combined to achieve a wide resolution range from atomic to sub-nano resolutions, making correlative microscopy an emerging trend. The developments in microscopic methods provide multi-fold and spatial information, advancing our understanding of viral infections and providing critical tools for developing novel antiviral strategies and rapid responses to emerging viral threats.
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(This article belongs to the Special Issue Microscopy Methods for Virus Research)
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Open AccessArticle
N-Acetylcysteine Inhibits Coxsackievirus B3 Replication by Downregulating Eukaryotic Translation Elongation Factor 1 Alpha 1
by
Yao Wang, Tian Luan, Lixin Wang, Danxiang Feng, Yanyan Dong, Siwei Li, Hong Yang, Yang Chen, Yanru Fei, Lexun Lin, Jiahui Pan, Zhaohua Zhong and Wenran Zhao
Viruses 2024, 16(9), 1503; https://doi.org/10.3390/v16091503 - 23 Sep 2024
Abstract
Group B Coxsackieviruses (CVB) are one of the causative pathogens of myocarditis, which may progress to cardiomyopathy. The pathogenesis of CVB is not fully understood, and effective antiviral therapy is not available. N-acetylcysteine (NAC), the classic antioxidant, has been used in clinical practice
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Group B Coxsackieviruses (CVB) are one of the causative pathogens of myocarditis, which may progress to cardiomyopathy. The pathogenesis of CVB is not fully understood, and effective antiviral therapy is not available. N-acetylcysteine (NAC), the classic antioxidant, has been used in clinical practice for several decades to treat various medical conditions. In this study, the anti-CVB effect of NAC was investigated. We show that NAC dramatically suppressed viral replication and alleviated cardiac injury induced by CVB3. To further study the antiviral mechanism of NAC, RNA-sequencing was performed for CVB3-infected cells with NAC treatment. We found that eukaryotic elongation factor 1 alpha 1 (EEF1A1) is one of the most upregulated genes in CVB3-infected cells. However, EEF1A2, the highly homologous isoform of EEF1A1, remains unchanged. EEF1A1 expression was significantly suppressed by NAC treatment in CVB3-infected cells, while EEF1A2 was not affected. eEF1A1 knockdown significantly inhibited CVB3 replication, implicating that eEF1A1 facilitates viral replication. Importantly, we show that eEF1A1, which was not expressed in the myocardia of newborn mice, was significantly upregulated by CVB3 infection. NAC markedly downregulated the expression of eEF1A1 but not eEF1A2 in the myocardia of CVB3-infected mice. Furthermore, NAC accelerated eEF1A1 degradation by promoting autophagy in CVB3-infected cells. We show that p62, one of the critical adaptors of autophagic targets, interacts with eEF1A1 and was downregulated in CVB3-infected cells upon NAC treatment. Taken together, this study demonstrated that NAC shows a potent anti-CVB effect through the downregulation of eEF1A1.
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(This article belongs to the Special Issue Innovative Drug Discovery for Emerging Viral Diseases)
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Open AccessBrief Report
Evaluation of the Deletion of African Swine Fever Virus E111R Gene from the Georgia Isolate in Virus Replication and Virulence in Domestic Pigs
by
Elizabeth Ramirez-Medina, Lauro Velazquez-Salinas, Alyssa Valladares, Amanda Meyers, Leeanna Burton, Ediane Silva, Jason Clark, Manuel V. Borca and Douglas P. Gladue
Viruses 2024, 16(9), 1502; https://doi.org/10.3390/v16091502 - 23 Sep 2024
Abstract
African swine fever virus (ASFV) is the causative agent of an often lethal disease in domestic pigs, African swine fever (ASF). ASF is currently a pandemic disease challenging pig production in Eurasia. While the ASFV genome encodes for over 160 proteins, the function
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African swine fever virus (ASFV) is the causative agent of an often lethal disease in domestic pigs, African swine fever (ASF). ASF is currently a pandemic disease challenging pig production in Eurasia. While the ASFV genome encodes for over 160 proteins, the function of most of them are still not characterized. Among those ASF genes with unknown functions is the E111R gene. It has been recently reported that the deletion of the E111R gene from the genome of the virulent Chinese field isolate SY18 strain produced a reduction of virus virulence when pigs were inoculated at relatively low doses. Conversely, we report here that deletion of the ASFV gene E111R in the Georgia 2010 isolate does not alter the virulence of the parental virus in experimentally inoculated pigs. A recombinant virus lacking the E111R gene, ASFV-G-∆E111R was intramuscularly (IM) inoculated in domestic pigs at a dose of 102 HAD50 of ASFV-G-∆E111R and compared with animals that received a similar dose of virulent ASFV-G. Both, animals inoculated with either the recombinant ASFV-G-∆E111R or the parental virus developed a fatal form of the disease and were euthanized around the 6th–7th day post-inoculation (dpi).
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(This article belongs to the Special Issue African Swine Fever Virus 4.0)
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Evaluating the Use of Sacran, a Polysaccharide Isolated from Aphanothece sacrum, as a Possible Microbicide for Preventing HIV-1 Infection
by
Kouki Matsuda, Ryusho Kariya, Kenji Maeda and Seiji Okada
Viruses 2024, 16(9), 1501; https://doi.org/10.3390/v16091501 - 23 Sep 2024
Abstract
Since combination antiretroviral therapy (cART) was introduced to treat human immunodeficiency virus type-1 (HIV-1)/acquired immunodeficiency syndrome (AIDS), the AIDS mortality rate has markedly decreased, and convalescence in individuals with HIV has improved drastically. However, sexual transmission has made HIV-1 a global epidemic. Sacran
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Since combination antiretroviral therapy (cART) was introduced to treat human immunodeficiency virus type-1 (HIV-1)/acquired immunodeficiency syndrome (AIDS), the AIDS mortality rate has markedly decreased, and convalescence in individuals with HIV has improved drastically. However, sexual transmission has made HIV-1 a global epidemic. Sacran is a megamolecular polysaccharide extracted from cyanobacterium Aphanothece sacrum that exhibits numerous desirable characteristics for transdermic applications, such as safety as a biomaterial, a high moisture retention effect, the ability to form a film and hydrogel, and an anti-inflammatory effect. In this study, we evaluated the anti-HIV-1 effects in sacran as a barrier to HIV-1 transmission. Sacran inhibited HIV-1 infection and envelope-dependent cell-to-cell fusion. Moreover, we used a Transwell assay to confirm that sacran inhibited viral diffusion and captured viruses. The synergistic effects of sacran and other anti-HIV infection drugs were also evaluated. HIV-1 infections can be reduced through the synergistic effects of sacran and anti-HIV-1 drugs. Our study suggests using sacran gel to provide protection against HIV-1 transmission.
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(This article belongs to the Section Human Virology and Viral Diseases)
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