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Genetic and Molecular Characterization of Avian Influenza A(H9N2) Viruses from Live Bird Markets (LBM) in Senegal.
IF 3.8 3区 医学
Viruses-Basel Pub Date : 2025-01-08 DOI: 10.3390/v17010073
Mamadou Malado Jallow, Moussa Moise Diagne, Marie Henriette Dior Ndione, Mamadou Aliou Barry, Ndiendé Koba Ndiaye, Davy Evrard Kiori, Marie Pedapa Mendy, Déborah Goudiaby, Gamou Fall, Malick Fall, Ndongo Dia
{"title":"Genetic and Molecular Characterization of Avian Influenza A(H9N2) Viruses from Live Bird Markets (LBM) in Senegal.","authors":"Mamadou Malado Jallow, Moussa Moise Diagne, Marie Henriette Dior Ndione, Mamadou Aliou Barry, Ndiendé Koba Ndiaye, Davy Evrard Kiori, Marie Pedapa Mendy, Déborah Goudiaby, Gamou Fall, Malick Fall, Ndongo Dia","doi":"10.3390/v17010073","DOIUrl":"10.3390/v17010073","url":null,"abstract":"<p><p>Despite extensive experience with influenza surveillance in humans in Senegal, there is limited knowledge about the actual situation and genetic diversity of avian influenza viruses (AIVs) circulating in the country, hindering control measures and pandemic risk assessment. Therefore, as part of the \"One Health\" approach to influenza surveillance, we conducted active AIV surveillance in two live bird markets (LBMs) in Dakar to better understand the dynamics and diversity of influenza viruses in Senegal, obtain genetic profiles of circulating AIVs, and assess the risk of emergence of novel strains and their transmission to humans. Cloacal swabs from poultry and environmental samples collected weekly from the two LBMs were screened by RT-qPCR for H5, H7, and H9 AIVs. Subsequently, a subset of H9-positive samples was selected for whole sequencing. From December 2023 to October 2024, 499 samples were tested, and AIV was detected in 58.3% of them. Among these, A/H9N2 was the only subtype detected in both markets, with a detection rate of 47.7% (82/172) in Thiaroye and 35.3% (42/119) in Tilene, resulting in an overall positivity rate of 42.6% (124/291). Genome sequencing of 22 A/H9N2 isolates, including 11 poultry drinking water samples, 7 carcass wash water samples, 3 fecal samples, and 1 cloacal swab, yielded 7 complete and 15 partial genomic sequences. Phylogenetic analyses of the resulting sequences showed that the A/H9N2 isolates obtained in this study formed a monophyletic cluster and were closely related to the Senegalese human strain (A/Senegal/0243/2019) identified through the national influenza sentinel surveillance program. These strains were also closely related to the A/H9N2 viruses of the G1 lineage circulating in neighboring countries, suggesting cross-border transmission. The A/H9N2 strains carried the low pathogenicity RSSR/GLF motif at the HA cleavage site and possessed several key amino acid mutations, including HA-I155T and HA-Q226L, which are associated with human host adaptation, PB2-T105V, PB2-A661T, and PB2-A588V, which are linked to the human-to-human transmission and increased polymerase activity, NS2-T14M, NS2-M100I, NS1-I106M, NS1-V222M, NS1-E223A, NS1-I226V, NS1-E227G, and NS1-P228S, which are known to alter virulence (increased or reduced) in humans or mice, and M2-S31N, which promotes drug resistance. Seven potential N-glycosylation sites were predicted in the HA protein and six in the NA protein. The selection pressure analysis revealed that the A/H9N2 isolates were primarily under neutral evolution or purifying selection pressure. Overall, our findings highlight the potential for cross-species transmission of Senegalese A/H9N2 viruses, emphasizing the need for sustained monitoring of these viruses in both animal and human populations.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Comprehensive Review of the Development and Therapeutic Use of Antivirals in Flavivirus Infection.
IF 3.8 3区 医学
Viruses-Basel Pub Date : 2025-01-08 DOI: 10.3390/v17010074
Aarti Tripathi, Shailendra Chauhan, Renu Khasa
{"title":"A Comprehensive Review of the Development and Therapeutic Use of Antivirals in Flavivirus Infection.","authors":"Aarti Tripathi, Shailendra Chauhan, Renu Khasa","doi":"10.3390/v17010074","DOIUrl":"10.3390/v17010074","url":null,"abstract":"<p><p>Flaviviruses are a diverse group of viruses primarily transmitted through hematophagous insects like mosquitoes and ticks. Significant expansion in the geographic range, prevalence, and vectors of flavivirus over the last 50 years has led to a dramatic increase in infections that can manifest as hemorrhagic fever or encephalitis, leading to prolonged morbidity and mortality. Millions of infections every year pose a serious threat to worldwide public health, encouraging scientists to develop a better understanding of the pathophysiology and immune evasion mechanisms of these viruses for vaccine development and antiviral therapy. Extensive research has been conducted in developing effective antivirals for flavivirus. Various approaches have been extensively utilized in clinical trials for antiviral development, targeting virus entry, replication, polyprotein synthesis and processing, and egress pathways exploiting virus as well as host proteins. However, to date, no licensed antiviral drug exists to treat the diseases caused by these viruses. Understanding the mechanisms of host-pathogen interaction, host immunity, viral immune evasion, and disease pathogenesis is highly warranted to foster the development of antivirals. This review provides an extensively detailed summary of the most recent advances in the development of antiviral drugs to combat diseases.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structural Analysis of Inhibitor Binding to Enterovirus-D68 3C Protease.
IF 3.8 3区 医学
Viruses-Basel Pub Date : 2025-01-08 DOI: 10.3390/v17010075
Vincent N Azzolino, Ala M Shaqra, Akbar Ali, Nese Kurt Yilmaz, Celia A Schiffer
{"title":"Structural Analysis of Inhibitor Binding to Enterovirus-D68 3C Protease.","authors":"Vincent N Azzolino, Ala M Shaqra, Akbar Ali, Nese Kurt Yilmaz, Celia A Schiffer","doi":"10.3390/v17010075","DOIUrl":"10.3390/v17010075","url":null,"abstract":"<p><p>Enterovirus-D68 (EV68) continues to present as a global health issue causing respiratory illness and outbreaks associated with long-lasting neurological disease, with no antivirals or specific treatment options. The development of antiviral therapeutics, such as small-molecule inhibitors that target conserved proteins like the enteroviral 3C protease, remains to be achieved. While various 3C inhibitors have been investigated, their design does not consider the potential emergence of drug resistance mutations. For other antivirals where resistance has been a challenge, we have demonstrated that the likelihood of resistance can be minimized by designing inhibitors that leverage the evolutionary constraints of the target. Here, we characterize a series of 3C inhibitors against EV68-3C protease through enzyme inhibition, protein crystallography, and structural analysis. We have determined and analyzed three high-resolution inhibitor-bound crystal structures of EV68-3C protease, which revealed possible sites of resistance mutations, a key structural water molecule conserved during ligand binding, and the conformational flexibility of the catalytic histidine H40. This structural analysis combined with enzymatic assays provides insights for the rational design of inhibitors that are robust against resistance toward developing antiviral treatments for EV68 infections.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Emerging Roles of TRIM56 in Antiviral Innate Immunity.
IF 3.8 3区 医学
Viruses-Basel Pub Date : 2025-01-07 DOI: 10.3390/v17010072
Dang Wang, Kui Li
{"title":"Emerging Roles of TRIM56 in Antiviral Innate Immunity.","authors":"Dang Wang, Kui Li","doi":"10.3390/v17010072","DOIUrl":"10.3390/v17010072","url":null,"abstract":"<p><p>The tripartite-motif protein 56 (TRIM56) is a RING-type E3 ubiquitin ligase whose functions were recently beginning to be unveiled. While the physiological role(s) of TRIM56 remains unclear, emerging evidence suggests this protein participates in host innate defense mechanisms that guard against viral infections. Interestingly, TRIM56 has been shown to pose a barrier to viruses of distinct families by utilizing its different domains. Apart from exerting direct, restrictive effects on viral propagation, TRIM56 is implicated in regulating innate immune signaling pathways that orchestrate type I interferon response or autophagy, through which it indirectly impacts viral fitness. Remarkably, depending on viral infection settings, TRIM56 either operates in a canonical, E3 ligase-dependent fashion or adopts an enzymatically independent, non-canonical mechanism to bolster innate immune signaling. Moreover, the recent revelation that TRIM56 is an RNA-binding protein sheds new light on its antiviral mechanisms against RNA viruses. This review summarizes recent advances in the emerging roles of TRIM56 in innate antiviral immunity. We focus on its direct virus-restricting effects and its influence on innate immune signaling through two critical pathways: the endolysosome-initiated, double-stranded RNA-sensing TLR3-TRIF pathway and the cytosolic DNA-sensing, cGAS-STING pathway. We discuss the underpinning mechanisms of action and the questions that remain. Further studies understanding the complexity of TRIM56 involvement in innate immunity will add to critical knowledge that could be leveraged for developing antiviral therapeutics.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Conserved Nuclear Localization Signal in NS2 Protein of Bombyx Mori Bidensovirus: A Potential Invertebrate ssDNA Virus Trait.
IF 3.8 3区 医学
Viruses-Basel Pub Date : 2025-01-06 DOI: 10.3390/v17010071
Qian Yu, Jiaxin Yan, Ying Chen, Jinfeng Zhang, Qi Tang, Feifei Zhu, Lindan Sun, Shangshang Ma, Xiaoyong Liu, Keping Chen, Qin Yao
{"title":"Conserved Nuclear Localization Signal in NS2 Protein of Bombyx Mori Bidensovirus: A Potential Invertebrate ssDNA Virus Trait.","authors":"Qian Yu, Jiaxin Yan, Ying Chen, Jinfeng Zhang, Qi Tang, Feifei Zhu, Lindan Sun, Shangshang Ma, Xiaoyong Liu, Keping Chen, Qin Yao","doi":"10.3390/v17010071","DOIUrl":"10.3390/v17010071","url":null,"abstract":"<p><p>Bombyx mori bidensovirus (BmBDV), a significant pathogen in the sericulture industry, holds a unique taxonomic position due to its distinct segmented single-stranded DNA (ssDNA) genome and the presence of a self-encoding DNA polymerase. However, the functions of viral non-structural proteins, such as NS2, remain unknown. This protein is hypothesized to play a role in viral replication and pathogenesis. To investigate its structure and function, we employed phylogenetic analysis, subcellular localization, mutational analysis, and a dual-luciferase reporter system to characterize the nuclear localization signal (NLS) within NS2 and its effect on viral promoter activity. Additionally, co-immunoprecipitation and mass spectrometry were utilized to identify host proteins interacting with NS2. We identified a functional bipartite NLS in NS2, validated the combination pattern of key amino acids, and demonstrated its role in regulating viral promoter activity. Furthermore, we identified potential NLSs in NS2 homologs in other invertebrate ssDNA viruses based on sequence analysis. We also revealed interactions between NS2 and host nuclear transport proteins, suggesting that it plays a role in nuclear transport and viral replication. This research underscores the importance of NS2's NLS in BmBDV's life cycle and its potential conservation across invertebrate ssDNA viruses, providing insights into virus-host interactions and avenues for antiviral strategy development.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bacteriophage and Phage-Encoded Depolymerase Exhibit Antibacterial Activity Against K9-Type Acinetobacter baumannii in Mouse Sepsis and Burn Skin Infection Models.
IF 3.8 3区 医学
Viruses-Basel Pub Date : 2025-01-06 DOI: 10.3390/v17010070
Alexander I Borzilov, Nikolay V Volozhantsev, Olga V Korobova, Lyubov V Kolupaeva, Evgenia S Pereskokova, Tatiana I Kombarova, Mikhail M Shneider, Konstantin A Miroshnikov, Ivan A Dyatlov, Anastasia V Popova
{"title":"Bacteriophage and Phage-Encoded Depolymerase Exhibit Antibacterial Activity Against K9-Type <i>Acinetobacter baumannii</i> in Mouse Sepsis and Burn Skin Infection Models.","authors":"Alexander I Borzilov, Nikolay V Volozhantsev, Olga V Korobova, Lyubov V Kolupaeva, Evgenia S Pereskokova, Tatiana I Kombarova, Mikhail M Shneider, Konstantin A Miroshnikov, Ivan A Dyatlov, Anastasia V Popova","doi":"10.3390/v17010070","DOIUrl":"10.3390/v17010070","url":null,"abstract":"<p><p><i>Acinetobacter baumannii</i> is a widely distributed nosocomial pathogen that causes various acute and chronic infections, particularly in immunocompromised patients. In this study, the activities of the K9-specific virulent phage AM24 and phage-encoded depolymerase DepAPK09 were assessed using in vivo mouse sepsis and burn skin infection models. In the mouse sepsis model, in the case of prevention or early treatment, a single K9-specific phage or recombinant depolymerase injection was able to protect 100% of the mice after parenteral infection with a lethal dose of <i>A. baumannii</i> of the K9-type, with complete eradication of the pathogen. In the case of delayed treatment, mouse survival decreased to 70% when injected with the phage and to 40% when treated with the recombinant enzyme. In the mouse burn skin infection model, the number of <i>A. baumannii</i> cells on the surface of the wound and in the deep layers of the skin decreased by several-fold after treatment with both the K9-specific phage and the recombinant depolymerase. The phage and recombinant depolymerase were highly stable and retained activity under a wide range of temperatures and pH values. The results obtained contribute to expanding our understanding of the in vivo therapeutic potential of specific phages and phage-derived depolymerases interacting with <i>A. baumannii</i> of different capsular types.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Functional Verification of Differentially Expressed Genes Following DENV2 Infection in Aedes aegypti.
IF 3.8 3区 医学
Viruses-Basel Pub Date : 2025-01-06 DOI: 10.3390/v17010067
Xiaoli Chen, Xinyu Zhou, Xiaoxue Xie, Bo Li, Teng Zhao, Haotian Yu, Dan Xing, Jiahong Wu, Chunxiao Li
{"title":"Functional Verification of Differentially Expressed Genes Following DENV2 Infection in <i>Aedes aegypti</i>.","authors":"Xiaoli Chen, Xinyu Zhou, Xiaoxue Xie, Bo Li, Teng Zhao, Haotian Yu, Dan Xing, Jiahong Wu, Chunxiao Li","doi":"10.3390/v17010067","DOIUrl":"10.3390/v17010067","url":null,"abstract":"<p><p>The dengue virus (DENV) is primarily transmitted by <i>Aedes aegypti</i>. Investigating genes associated with mosquito susceptibility to DENV2 offers a theoretical foundation for targeted interventions to regulate or block viral replication and transmission within mosquitoes. Based on the transcriptomic analyses of the midgut and salivary glands from <i>Aedes aegypti</i> infected with DENV2, alongside analyses of Aag2 cell infections, 24 genes potentially related to the regulation of <i>Aedes aegypti</i> infection with DENV2 were selected. By establishing transient transfection and overexpression models of <i>Aedes aegypti</i> Aag2 cells, and mosquito target gene interference models, the difference in viral load before and after treatment was compared, and the effects of DEGs on viral replication were evaluated. After overexpressing 24 DEGs in Aag2 cells, 19 DEGs showed a significant difference in DENV2 RNA copies in the cell supernatant (<i>p</i> < 0.05). In adult mosquitoes, knocking down defensin-A, defensin-A-like, and SMCT1 respectively reduced the DENV2 RNA copies, while knocking down UGT2B1 and ND4 respectively increased the DENV2 RNA copies. In this study, to assess the role of genes related to DENV2 replication, and transient transfection and overexpression models in Aag2 cells and mosquito gene knockdown models were established, and five genes, defensin-A, defensin-A-like, SMCT1, UGT2B1, and ND4, were found to have an impact on the replication of DENV2, providing a reference basis for studying the complex mechanism of mosquito-virus interactions.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tenofovir and Doravirine Are Potential Reverse-Transcriptase Analogs in Combination with the New Reverse-Transcriptase Translocation Inhibitor (Islatravir) Among Treatment-Experienced Patients in Cameroon: Designing Future Treatment Strategies for Low- and Middle-Income Countries.
IF 3.8 3区 医学
Viruses-Basel Pub Date : 2025-01-06 DOI: 10.3390/v17010069
Alex Durand Nka, Yagai Bouba, Wilfried Rooker Tsapi Lontsi, Davy-Hyacinte Gouissi Anguechia, Georges Teto, Aude Christelle Ka'e, Ezechiel Ngoufack Jagni Semengue, Collins Ambe Chenwi, Désiré Takou, Lum Forgwei, Tatiana Anim-Keng Tekoh, Aurelie Minelle Kengni Ngueko, Bernadette Bomgning Fokou, Jeremiah Efakika Gabisa, Michel Carlos Tommo Tchouaket, Willy Leroi TognaPabo, Derrick Tambe Ayuk Ngwese, Jacky Njiki Bikoi, Daniele Armenia, Vittorio Colizzi, Marcel Yotebieng, Nicaise Ndembi, Maria-Mercedes Santoro, Francesca Ceccherini-Silberstein, Carlo-Federico Perno, Alexis Ndjolo, Joseph Fokam
{"title":"Tenofovir and Doravirine Are Potential Reverse-Transcriptase Analogs in Combination with the New Reverse-Transcriptase Translocation Inhibitor (Islatravir) Among Treatment-Experienced Patients in Cameroon: Designing Future Treatment Strategies for Low- and Middle-Income Countries.","authors":"Alex Durand Nka, Yagai Bouba, Wilfried Rooker Tsapi Lontsi, Davy-Hyacinte Gouissi Anguechia, Georges Teto, Aude Christelle Ka'e, Ezechiel Ngoufack Jagni Semengue, Collins Ambe Chenwi, Désiré Takou, Lum Forgwei, Tatiana Anim-Keng Tekoh, Aurelie Minelle Kengni Ngueko, Bernadette Bomgning Fokou, Jeremiah Efakika Gabisa, Michel Carlos Tommo Tchouaket, Willy Leroi TognaPabo, Derrick Tambe Ayuk Ngwese, Jacky Njiki Bikoi, Daniele Armenia, Vittorio Colizzi, Marcel Yotebieng, Nicaise Ndembi, Maria-Mercedes Santoro, Francesca Ceccherini-Silberstein, Carlo-Federico Perno, Alexis Ndjolo, Joseph Fokam","doi":"10.3390/v17010069","DOIUrl":"10.3390/v17010069","url":null,"abstract":"<p><p>Islatravir (ISL) is a novel antiretroviral that inhibits HIV-1 reverse transcriptase translocation. The M184V mutation, known to reduce ISL's viral susceptibility in vitro, could arise from prolonged exposure to nucleoside reverse transcriptase inhibitors (NRTI) (3TC). This study evaluated the predictive efficacy of ISL and identified potentially active antiretrovirals in combination among treatment-experienced patients in Cameroon, where NRTIs (3TC) have been the backbone of ART for decades now. Although ISL is a long-acting antiretroviral, it will provide other therapeutic options in combination with other reverse transcriptase inhibitors that remain effective. We analyzed 1170 HIV-1 sequences from patients failing first-, second-, and third-line ART using the CIRCB Antiviral Resistance Evaluation (CIRCB-CARE) database. Drug resistance mutations (DRMs) were interpreted using Stanford HIVdb.v9, and covariation patterns between M184V and major NRTI/NNRTI DRMs were assessed. The study population, with a median age of 40 years, showed a high prevalence of resistance to NRTIs (77.4%) and NNRTIs (49.2%). The most frequent NRTI DRMs were M184V/I (83.3%), M41L (25.0%), and T215FY (36.8%), while common NNRTI DRMs included K103NS (53.3%), Y181CIV (27.7%), and G190ASE (22.2%). In first-line ART failure, M184V significantly covaried with K70R, L74I, and M41L for NRTIs and K103N and G190A for NNRTIs. In second-line failure, the covariation with M184V extended to T215Y, M41L, and D67N for NRTIs and G190A, K103N, and K103S for NNRTIs. No significant covariation with M184V was observed in third-line treatment failures. Based on these covariations and on the effect of these mutations on available anti-HIV drugs, TDF (partial efficacy) and Doravirine (fully active) were identified as potentially suitable candidates in combination with ISL among patients failing the first, second, and third lines, and could serve as a valuable therapeutic option in LMICs facing similar treatment challenges.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of COVID-19 on Ocular Surface Health: Infection Mechanisms, Immune Modulation, and Inflammatory Responses.
IF 3.8 3区 医学
Viruses-Basel Pub Date : 2025-01-06 DOI: 10.3390/v17010068
Duliurui Huang, Weixia Xuan, Zhijie Li
{"title":"Impact of COVID-19 on Ocular Surface Health: Infection Mechanisms, Immune Modulation, and Inflammatory Responses.","authors":"Duliurui Huang, Weixia Xuan, Zhijie Li","doi":"10.3390/v17010068","DOIUrl":"10.3390/v17010068","url":null,"abstract":"<p><p>COVID-19, caused by SARS-CoV-2, has presented formidable challenges to global health since its emergence in late 2019. While primarily known for respiratory symptoms, it can also affect the ocular surface. This review summarizes the effects of SARS-CoV-2 on ocular surface immunity and inflammation, focusing on infection mechanisms, immune responses, and clinical manifestations. Ocular symptoms, though uncommon, include conjunctivitis, dry eye, and blurred vision. SARS-CoV-2 binds to ACE2 receptors in ocular surface epithelial cells, facilitating viral entry, replication, and local dissemination. The innate immune responses involving corneal epithelial cells and immune cells are discussed, alongside mechanisms of antigen presentation and adaptive immunity. The review also examines the roles of cytokines and chemokines in mediating ocular surface inflammation and explores the impact of cytokine storms and chronic inflammation on ocular health. Additionally, the interplay between systemic and ocular immune responses is highlighted, analyzing how systemic COVID-19 inflammation influences ocular surface health. These insights underscore the broader implications of COVID-19 beyond localized ocular infection. By consolidating current findings, this review aims to guide preventive and therapeutic strategies while identifying directions for future research to mitigate the ocular consequences of COVID-19.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effect of Hepatitis E Virus on the Male Reproductive System: A Review of Current Evidence.
IF 3.8 3区 医学
Viruses-Basel Pub Date : 2025-01-05 DOI: 10.3390/v17010066
Ahmed A Kotb, Mohamed A El-Mokhtar, Ibrahim M Sayed
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