Frontiers in virology最新文献

{"title":"CD4+ T lymphocyte recovery in the modern antiretroviral therapy era: Toward a new threshold for defining immunological non-responders","authors":"L. Taramasso, L. Labate, F. Briano, G. Brucci, S. Mora, S. Blanchi, M. Giacomini, M. Bassetti, A. di Biagio","doi":"10.3389/fviro.2022.822153","DOIUrl":"https://doi.org/10.3389/fviro.2022.822153","url":null,"abstract":"Introduction Despite the high level of efficacy of modern antiretroviral therapy (ART) in reducing HIV viremia and the control of viral replication, some people living with HIV (PLWH) do not recover their CD4+ T cell count. Methods To evaluate the frequency and predictive factors of discordant immune responses, we performed a retrospective cohort study of 324 antiretroviral-naïve PLWH who initiated first-line ART between 2008 and 2018 and maintained HIV RNA < 50 copies/ml during 36 months of follow-up. PLWH were defined as immunological non-responders (INRs) when CD4+ T cell count was < 20% compared with baseline (INR20%), or < 500 cells/mm3 (INR500) or < 200 cells/mm3 (INR200) at 36 months. Results The prevalence of INR20%, INR500, and INR200 was 12.5%, 34.6%, and 1.5%, respectively. After adjustment for possible confounders, CD4 nadir showed a significant association with all INR definitions, with lower values predicting INR500 (aOR 0.98, 95% CI 0.98–0.99, p < 0.001) and INR200 (aOR 0.98, 95% CI 0.95–1.01, p = 0.096). Moreover, a higher baseline CD4/CD8 ratio was inversely related to the probability of being INR500 (OR 0.03, 95% CI 0.01–0.12, p < 0.001) and INR200 (OR 0.002, 95% CI 18–7–67.72, p = 0.255). By contrast, INR20% had a higher CD4 nadir and CD4/CD8 ratio than other INRs, suggesting the identification of an heterogenous population with such definition. Discussion The present study highlights how INR200 has become rare in the contemporary ART era, and about one-third of PLWH meet the criteria for INR500. Overcoming the threshold of 500 CD4/mm3 could be an appropriate definition of immune response, in contrast with the older definitions of INR200 and INR20%. Early diagnosis and rapid treatment initiation, before CD4 counts and the CD4/CD8 ratio begin to decline, are critical for achieving an optimal immune response.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42463113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In-depth genetic characterization of the SARS-CoV-2 pandemic in a two-year frame in North Macedonia using second and third generation sequencing technologies","authors":"Maja Vukovikj, Golubinka Boshevska, Elizabeta Janchevska, Teodora Buzharova, Ardian Preshova, Milica Simova, Aneta Peshnacka, Dragan Kocinski, G. Kuzmanovska, S. Memeti, I. Gjorgoski","doi":"10.3389/fviro.2022.1064882","DOIUrl":"https://doi.org/10.3389/fviro.2022.1064882","url":null,"abstract":"The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a persistent negative impact on both the public health and the global economy. To comprehend the origin, transmission routes and discover the mutations that alter the virus’s transmissibility and pathogenicity, full-length SARS-CoV-2 genomes have to be molecularly characterized. Focusing on a two-year time frame (2020-2021), we provide an in-depth virologic and epidemiological overview of the SARS-CoV-2 pandemic in the Republic of North Macedonia by assessing the frequency and distribution of the circulating SARS-CoV-2 variants. Using genetic characterization and phylogenetic analysis we shed light on the molecular evolution of the virus as well as test for a possible connection between specific SARS-CoV-2 haplotypes and the severity of the clinical symptoms. Our results show that one fifth (21.51%) of the tested respiratory samples for SARS-CoV-2 were positive. A noticeable trend in the incidence and severity of the COVID-19 infections was observed in the 60+ age group between males and females. Of the total number of positive cases, the highest incidence of SARS-CoV-2 was noticed in 60+ males (4,170.4/100,000), with a statistically significant (0,0001) difference between the two sexes. Additionally, a 1.8x increase in male mortality and consequentially significantly higher number of death cases was observed compared to females of the same age group (0.001). A total of 327 samples were sequenced in the period March 2020 - August 2021, showing the temporal distribution of SARS-CoV-2 variants circulating in North Macedonia. The phylogenetic analysis showed that most of the viral genomes were closely related and clustered in four distinctive lineages, B.1, B.1.1.7, B.1.351 and B.1.617.2. A statistically significant difference was observed in the 2C_1 haplotype (p=0.0013), where 10.5% of the patients were hospitalized due to severe clinical condition. By employing genetic sequencing, coupled with epidemiological investigations, we investigated viral distribution patterns, identified emerging variants and detected vaccine breakthrough infections. The present work is the first molecular study giving a comprehensive overview of the genetic landscape of circulating SARS-CoV-2 viruses in North Macedonia in a period of two years.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43036528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the immunogenicity and efficacy of an rVSV vaccine against Zika virus infection in macaca nemestrina.","authors":"Jennifer Tisoncik-Go, Kathleen M Voss, Thomas B Lewis, Antonio E Muruato, LaRene Kuller, Eric E Finn, Dillon Betancourt, Solomon Wangari, Joel Ahrens, Naoto Iwayama, Richard F Grant, Robert D Murnane, Paul T Edlefsen, Deborah H Fuller, Glen N Barber, Michael Gale, Megan A O'Connor","doi":"10.3389/fviro.2023.1108420","DOIUrl":"10.3389/fviro.2023.1108420","url":null,"abstract":"<p><p>Zika virus (ZIKV) is a mosquito-borne flavivirus that causes an acute febrile illness. ZIKV can be transmitted between sexual partners and from mother to fetus. Infection is strongly associated with neurologic complications in adults, including Guillain-Barré syndrome and myelitis, and congenital ZIKV infection can result in fetal injury and congenital Zika syndrome (CZS). Development of an effective vaccine is imperative to protect against ZIKV vertical transmission and CZS. Recombinant Vesicular Stomatitis virus (rVSV) is a highly effective and safe vector for the delivery of foreign immunogens for vaccine purposes. Here, we evaluate an rVSV vaccine expressing the full length pre-membrane (prM) and ZIKV envelope (E) proteins (VSV-ZprME), shown to be immunogenic in murine models of ZIKV infection, for its capacity to induce immune responses in nonhuman primates. Moreover, we assess the efficacy of the rVSVΔM-ZprME vaccine in the protection of pigtail macaques against ZIKV infection. Administration of the rVSVΔM-ZprME vaccine was safe, but it did not induce robust anti-ZIKV T-cell responses, IgM or IgG antibodies, or neutralizing antibodies in most animals. Post ZIKV challenge, animals that received the rVSVΔM control vaccine lacking ZIKV antigen had higher levels of plasma viremia compared to animals that received the rVSVΔM-ZprME vaccine. Anti-ZIKV neutralizing Ab titers were detected in a single animal that received the rVSVΔM-ZprME vaccine that was associated with reduced plasma viremia. The overall suboptimal ZIKV-specific cellular and humoral responses post-immunization indicates the rVSVΔM-ZprME vaccine did not elicit an immune response in this pilot study. However, recall antibody response to the rVSVΔM-ZprME vaccine indicates it may be immunogenic and further developments to the vaccine construct could enhance its potential as a vaccine candidate in a nonhuman primate pre-clinical model.</p>","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":"3 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10306241/pdf/nihms-1902797.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9734866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling of vertical transmission and pathogenesis of cytomegalovirus in pregnancy: Opportunities and challenges.","authors":"Gregory W Kirschen,&nbsp;Irina Burd","doi":"10.3389/fviro.2023.1106634","DOIUrl":"https://doi.org/10.3389/fviro.2023.1106634","url":null,"abstract":"<p><p>In addition to facilitating nutrient, oxygen, and waste transfer between developing fetus and mother, the placenta provides important immune barrier function against infection. Elucidation of the complexity of placental barrier function at the maternal-fetal interface has been greatly aided through experimental model organism systems. In this review, we focus on models of vertical transmission of cytomegalovirus (CMV), a ubiquitous double-stranded DNA viruses whose vertical transmission during pregnancy can lead to devastating neurological and obstetric sequelae. We review the current evidence related to guinea pig and murine models of congenital CMV infection, discuss the possible translatability of a non-human primate model, and conclude with recently developed technology using human placental organoids.</p>","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":"3 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9997718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9108228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renewed global threat by the novel SARS-CoV-2 variants ‘XBB, BF.7, BQ.1, BA.2.75, BA.4.6’: A discussion","authors":"R. Mohapatra, A. Mahal, L. Kutikuppala, Madhumita Pal, V. Kandi, A. Sarangi, Ahmad J. Obaidullah, Snehasis Mishra","doi":"10.3389/fviro.2022.1077155","DOIUrl":"https://doi.org/10.3389/fviro.2022.1077155","url":null,"abstract":"COPYRIGHT © 2022 Mohapatra, Mahal, Kutikuppala, Pal, Kandi, Sarangi, Obaidullah and Mishra. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. TYPE Opinion PUBLISHED 23 December 2022 DOI 10.3389/fviro.2022.1077155","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49586896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diverse roles of heterogeneous nuclear ribonucleoproteins in viral life cycle","authors":"Krishna Bhattarai, M. Holcik","doi":"10.3389/fviro.2022.1044652","DOIUrl":"https://doi.org/10.3389/fviro.2022.1044652","url":null,"abstract":"Understanding the host-virus interactions helps to decipher the viral replication strategies and pathogenesis. Viruses have limited genetic content and rely significantly on their host cell to establish a successful infection. Viruses depend on the host for a broad spectrum of cellular RNA-binding proteins (RBPs) throughout their life cycle. One of the major RBP families is the heterogeneous nuclear ribonucleoproteins (hnRNPs) family. hnRNPs are typically localized in the nucleus, where they are forming complexes with pre-mRNAs and contribute to many aspects of nucleic acid metabolism. hnRNPs contain RNA binding motifs and frequently function as RNA chaperones involved in pre-mRNA processing, RNA splicing, and export. Many hnRNPs shuttle between the nucleus and the cytoplasm and influence cytoplasmic processes such as mRNA stability, localization, and translation. The interactions between the hnRNPs and viral components are well-known. They are critical for processing viral nucleic acids and proteins and, therefore, impact the success of the viral infection. This review discusses the molecular mechanisms by which hnRNPs interact with and regulate each stage of the viral life cycle, such as replication, splicing, translation, and assembly of virus progeny. In addition, we expand on the role of hnRNPs in the antiviral response and as potential targets for antiviral drug research and development.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47610739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytoplasmic ribonucleoprotein complexes, RNA helicases and coronavirus infection","authors":"Li Wang, M. Guzman, I. Sola, L. Enjuanes, S. Zúñiga","doi":"10.3389/fviro.2022.1078454","DOIUrl":"https://doi.org/10.3389/fviro.2022.1078454","url":null,"abstract":"RNA metabolism in the eukaryotic cell includes the formation of ribonucleoprotein complexes (RNPs) that, depending on their protein components, have a different function. Cytoplasmic RNPs, such as stress granules (SGs) or P-bodies (PBs) are quite relevant during infections modulating viral and cellular RNA expression and as key players in the host cell antiviral response. RNA helicases are abundant components of RNPs and could have a significant effect on viral infection. This review focuses in the role that RNPs and RNA helicases have during coronavirus (CoVs) infection. CoVs are emerging highly pathogenic viruses with a large single-stranded RNA genome. During CoV infection, a complex network of RNA-protein interactions in different RNP structures is established. In general, RNA helicases and RNPs have an antiviral function, but there is limited knowledge on whether the viral protein interactions with cell components are mediators of this antiviral effect or are part of the CoV antiviral counteraction mechanism. Additional data is needed to elucidate the role of these RNA-protein interactions during CoV infection and their potential contribution to viral replication or pathogenesis.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47348842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The host tRNA epitranscriptome: A new player in RNA virus infections","authors":"Marc Tallo-Parra, Elena Muscolino, J. Díez","doi":"10.3389/fviro.2022.1073619","DOIUrl":"https://doi.org/10.3389/fviro.2022.1073619","url":null,"abstract":"Viruses completely depend on the host translation machineries to express the viral proteins. Recent data reveal an unprecedented interaction of positive strand RNA ((+)RNA) viruses with the host tRNA epitranscriptome to favor viral protein expression via a specific reprogramming of codon optimality that ultimately favors decoding of the viral codons. We propose that this feature is shared by multiple RNA viruses and that the involved tRNA modifying enzymes represent promising novel targets for the development of broad-spectrum antivirals.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43595087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARSNTdb database: Factors affecting SARS-CoV-2 sequence conservation","authors":"John J Orgera, James J. Kelley, Omri Bar, Sathyanarayanan Vaidhyanathan, A. Grigoriev","doi":"10.3389/fviro.2022.1028335","DOIUrl":"https://doi.org/10.3389/fviro.2022.1028335","url":null,"abstract":"SARSNTdb offers a curated, nucleotide-centric database for users of varying levels of SARS-CoV-2 knowledge. Its user-friendly interface enables querying coding regions and coordinate intervals to find out the various functional and selective constraints that act upon the corresponding nucleotides and amino acids. Users can easily obtain information about viral genes and proteins, functional domains, repeats, secondary structure formation, intragenomic interactions, and mutation prevalence. Currently, many databases are focused on the phylogeny and amino acid substitutions, mainly in the spike protein. We took a novel, more nucleotide-focused approach as RNA does more than just code for proteins and many insights can be gleaned from its study. For example, RNA-targeted drug therapies for SARS-CoV-2 are currently being developed and it is essential to understand the features only visible at that level. This database enables the user to identify regions that are more prone to forming secondary structures that drugs can target. SARSNTdb also provides illustrative mutation data from a subset of ~25,000 patient samples with a reliable read coverage across the whole genome (from different locations and time points in the pandemic. Finally, the database allows for comparing SARS-CoV-2 and SARS-CoV domains and sequences. SARSNTdb can serve the research community by being a curated repository for information that gives a jump start to analyze a mutation’s effect far beyond just determining synonymous/non-synonymous substitutions in protein sequences.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43196008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overview of how HCMV manipulation of host cell intracellular trafficking networks can promote productive infection","authors":"Bailey S. Mosher, T. Kowalik, A. Yurochko","doi":"10.3389/fviro.2022.1026452","DOIUrl":"https://doi.org/10.3389/fviro.2022.1026452","url":null,"abstract":"Human cytomegalovirus (HCMV) is a significant cause of morbidity and mortality in the immunocompromised and developing fetuses. Infection has also been linked to chronic inflammatory diseases, cardiovascular disease, and the development of certain cancers. The wide range of pathologies associated with HCMV infection is attributable to the broad cellular tropism of the virus where infection affects every organ system. Like other viruses, HCMV must tailor host cells to support productive infection. In particular, HCMV dedicates many resources and various strategies to manipulate host intracellular trafficking networks to facilitate various aspects of infection across all infected cell types. The dysregulation of host intracellular trafficking networks allows the virus to translocate to the host cell nucleus for genome replication, facilitate nuclear import/export of viral proteins and immature virions, subvert the host immune response, form new organelles for progeny virion assembly, maturation and egress, and promote cellular migration and viral spread. However, due to their complex nature, many aspects of these processes are not well-studied. New research and omics-based technologies have recently begun to elucidate the extent to which HCMV dysregulates host cell trafficking machinery. Here we review the variety of strategies HCMV utilizes to dysregulate intracellular trafficking networks to promote productive infection.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45776117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}