Pub Date : 2023-09-29DOI: 10.1146/annurev-vi-10-102822-100111
Lynn W Enquist
{"title":"The Times They Are a-Changing.","authors":"Lynn W Enquist","doi":"10.1146/annurev-vi-10-102822-100111","DOIUrl":"10.1146/annurev-vi-10-102822-100111","url":null,"abstract":"","PeriodicalId":48761,"journal":{"name":"Annual Review of Virology","volume":null,"pages":null},"PeriodicalIF":11.3,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40487522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-29Epub Date: 2023-04-11DOI: 10.1146/annurev-virology-111821-103452
Caleb J Studstill, Cary A Moody
High-risk human papillomaviruses (HPVs) are associated with several human cancers. HPVs are small, DNA viruses that rely on host cell machinery for viral replication. The HPV life cycle takes place in the stratified epithelium, which is composed of different cell states, including terminally differentiating cells that are no longer active in the cell cycle. HPVs have evolved mechanisms to persist and replicate in the stratified epithelium by hijacking and modulating cellular pathways, including the DNA damage response (DDR). HPVs activate and exploit DDR pathways to promote viral replication, which in turn increases the susceptibility of the host cell to genomic instability and carcinogenesis. Here, we review recent advances in our understanding of the regulation of the host cell DDR by high-risk HPVs during the viral life cycle and discuss the potential cellular consequences of modulating DDR pathways.
{"title":"For Better or Worse: Modulation of the Host DNA Damage Response by Human Papillomavirus.","authors":"Caleb J Studstill, Cary A Moody","doi":"10.1146/annurev-virology-111821-103452","DOIUrl":"10.1146/annurev-virology-111821-103452","url":null,"abstract":"<p><p>High-risk human papillomaviruses (HPVs) are associated with several human cancers. HPVs are small, DNA viruses that rely on host cell machinery for viral replication. The HPV life cycle takes place in the stratified epithelium, which is composed of different cell states, including terminally differentiating cells that are no longer active in the cell cycle. HPVs have evolved mechanisms to persist and replicate in the stratified epithelium by hijacking and modulating cellular pathways, including the DNA damage response (DDR). HPVs activate and exploit DDR pathways to promote viral replication, which in turn increases the susceptibility of the host cell to genomic instability and carcinogenesis. Here, we review recent advances in our understanding of the regulation of the host cell DDR by high-risk HPVs during the viral life cycle and discuss the potential cellular consequences of modulating DDR pathways.</p>","PeriodicalId":48761,"journal":{"name":"Annual Review of Virology","volume":null,"pages":null},"PeriodicalIF":11.3,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10956471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9283339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-29Epub Date: 2023-06-02DOI: 10.1146/annurev-virology-111821-123859
Axel A Guzmán-Solís, Miguel Alejandro Navarro, María C Ávila-Arcos, Daniel Blanco-Melo
Humans have battled viruses for millennia. However, directly linking the symptomatology of disease outbreaks to specific viral pathogens was not possible until the twentieth century. With the advent of the genomic era and the development of advanced protocols for isolation, sequencing, and analysis of ancient nucleic acids from diverse human remains, the identification and characterization of ancient viruses became feasible. Recent studies have provided invaluable information about past epidemics and made it possible to examine assumptions and inferences on the origin and evolution of certain viral families. In parallel, the study of ancient viruses also uncovered their importance in the evolution of the human lineage and their key roles in shaping major events in human history. In this review, we describe the strategies used for the study of ancient viruses, along with their limitations, and provide a detailed account of what past viral infections have revealed about human history. Expected final online publication date for the Annual Review of Virology, Volume 10 is September 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
{"title":"A Glimpse into the Past: What Ancient Viral Genomes Reveal About Human History.","authors":"Axel A Guzmán-Solís, Miguel Alejandro Navarro, María C Ávila-Arcos, Daniel Blanco-Melo","doi":"10.1146/annurev-virology-111821-123859","DOIUrl":"10.1146/annurev-virology-111821-123859","url":null,"abstract":"Humans have battled viruses for millennia. However, directly linking the symptomatology of disease outbreaks to specific viral pathogens was not possible until the twentieth century. With the advent of the genomic era and the development of advanced protocols for isolation, sequencing, and analysis of ancient nucleic acids from diverse human remains, the identification and characterization of ancient viruses became feasible. Recent studies have provided invaluable information about past epidemics and made it possible to examine assumptions and inferences on the origin and evolution of certain viral families. In parallel, the study of ancient viruses also uncovered their importance in the evolution of the human lineage and their key roles in shaping major events in human history. In this review, we describe the strategies used for the study of ancient viruses, along with their limitations, and provide a detailed account of what past viral infections have revealed about human history. Expected final online publication date for the Annual Review of Virology, Volume 10 is September 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.","PeriodicalId":48761,"journal":{"name":"Annual Review of Virology","volume":null,"pages":null},"PeriodicalIF":11.3,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9937232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-29Epub Date: 2023-07-05DOI: 10.1146/annurev-virology-111821-122539
Ida Bagus Andika, Mengyuan Tian, Ruiling Bian, Xinran Cao, Ming Luo, Hideki Kondo, Liying Sun
The large genetic and structural divergences between plants and fungi may hinder the transmission of viruses between these two kingdoms to some extent. However, recent accumulating evidence from virus phylogenetic analyses and the discovery of naturally occurring virus cross-infection suggest the occurrence of past and current transmissions of viruses between plants and plant-associated fungi. Moreover, artificial virus inoculation experiments showed that diverse plant viruses can multiply in fungi and vice versa. Thus, virus cross-infection between plants and fungi may play an important role in the spread, emergence, and evolution of both plant and fungal viruses and facilitate the interaction between them. In this review, we summarize current knowledge related to cross-kingdom virus infection in plants and fungi and further discuss the relevance of this new virological topic in the context of understanding virus spread and transmission in nature as well as developing control strategies for crop plant diseases.
{"title":"Cross-Kingdom Interactions Between Plant and Fungal Viruses.","authors":"Ida Bagus Andika, Mengyuan Tian, Ruiling Bian, Xinran Cao, Ming Luo, Hideki Kondo, Liying Sun","doi":"10.1146/annurev-virology-111821-122539","DOIUrl":"10.1146/annurev-virology-111821-122539","url":null,"abstract":"<p><p>The large genetic and structural divergences between plants and fungi may hinder the transmission of viruses between these two kingdoms to some extent. However, recent accumulating evidence from virus phylogenetic analyses and the discovery of naturally occurring virus cross-infection suggest the occurrence of past and current transmissions of viruses between plants and plant-associated fungi. Moreover, artificial virus inoculation experiments showed that diverse plant viruses can multiply in fungi and vice versa. Thus, virus cross-infection between plants and fungi may play an important role in the spread, emergence, and evolution of both plant and fungal viruses and facilitate the interaction between them. In this review, we summarize current knowledge related to cross-kingdom virus infection in plants and fungi and further discuss the relevance of this new virological topic in the context of understanding virus spread and transmission in nature as well as developing control strategies for crop plant diseases.</p>","PeriodicalId":48761,"journal":{"name":"Annual Review of Virology","volume":null,"pages":null},"PeriodicalIF":11.3,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10132341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-29Epub Date: 2023-07-05DOI: 10.1146/annurev-virology-111821-100816
Meta Volcic, Lisa Wiesmüller, Frank Kirchhoff
Human and simian immunodeficiency viruses (HIVs and SIVs, respectively) encode several small proteins (Vif, Vpr, Nef, Vpu, and Vpx) that are called accessory because they are not generally required for viral replication in cell culture. However, they play complex and important roles for viral immune evasion and spread in vivo. Here, we discuss the diverse functions and the relevance of the viral protein U (Vpu) that is expressed from a bicistronic RNA during the late stage of the viral replication cycle and found only in HIV-1 and closely related SIVs. It is well established that Vpu counteracts the restriction factor tetherin, mediates degradation of the primary viral CD4 receptors, and inhibits activation of the transcription factor nuclear factor kappa B. Recent studies identified additional activities and provided new insights into the sophisticated mechanisms by which Vpu enhances and prolongs the release of fully infectious viral particles. In addition, it has been shown that Vpu prevents superinfection not only by degrading CD4 but also by modulating DNA repair mechanisms to promote degradation of nuclear viral complementary DNA in cells that are already productively infected.
{"title":"Small but Highly Versatile: The Viral Accessory Protein Vpu.","authors":"Meta Volcic, Lisa Wiesmüller, Frank Kirchhoff","doi":"10.1146/annurev-virology-111821-100816","DOIUrl":"10.1146/annurev-virology-111821-100816","url":null,"abstract":"<p><p>Human and simian immunodeficiency viruses (HIVs and SIVs, respectively) encode several small proteins (Vif, Vpr, Nef, Vpu, and Vpx) that are called accessory because they are not generally required for viral replication in cell culture. However, they play complex and important roles for viral immune evasion and spread in vivo. Here, we discuss the diverse functions and the relevance of the viral protein U (Vpu) that is expressed from a bicistronic RNA during the late stage of the viral replication cycle and found only in HIV-1 and closely related SIVs. It is well established that Vpu counteracts the restriction factor tetherin, mediates degradation of the primary viral CD4 receptors, and inhibits activation of the transcription factor nuclear factor kappa B. Recent studies identified additional activities and provided new insights into the sophisticated mechanisms by which Vpu enhances and prolongs the release of fully infectious viral particles. In addition, it has been shown that Vpu prevents superinfection not only by degrading CD4 but also by modulating DNA repair mechanisms to promote degradation of nuclear viral complementary DNA in cells that are already productively infected.</p>","PeriodicalId":48761,"journal":{"name":"Annual Review of Virology","volume":null,"pages":null},"PeriodicalIF":11.3,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10132342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-29DOI: 10.1146/annurev-virology-040323-082822
Ana Beatriz Enriquez, Felipe Ten Caten, Khader Ghneim, Rafick-Pierre Sekaly, Ashish Arunkumar Sharma
Despite antiretroviral therapy (ART), people living with human immunodeficiency virus (HIV) (PLWH) continue to experience chronic inflammation and immune dysfunction, which drives the persistence of latent HIV and prevalence of clinical comorbidities. Elucidating the mechanisms that lead to suboptimal immunity is necessary for developing therapeutics that improve the quality of life of PLWH. Although previous studies have found associations between gut dysbiosis and immune dysfunction, the cellular/molecular cascades implicated in the manifestation of aberrant immune responses downstream of microbial perturbations in PLWH are incompletely understood. Recent literature has highlighted that two abundant metabolite families, short-chain fatty acids (SCFAs) and bile acids (BAs), play a crucial role in shaping immunity. These metabolites can be produced and/or modified by bacterial species that make up the gut microbiota and may serve as the causal link between changes to the gut microbiome, chronic inflammation, and immune dysfunction in PLWH. In this review, we discuss our current understanding of the role of the microbiome on HIV acquisition and latent HIV persistence despite ART. Further, we describe cellular/molecular cascades downstream of SCFAs and BAs that drive innate or adaptive immune responses responsible for promoting latent HIV persistence in PLWH. This knowledge can be used to advance HIV cure efforts.
{"title":"Regulation of Immune Homeostasis, Inflammation, and HIV Persistence by the Microbiome, Short-Chain Fatty Acids, and Bile Acids.","authors":"Ana Beatriz Enriquez, Felipe Ten Caten, Khader Ghneim, Rafick-Pierre Sekaly, Ashish Arunkumar Sharma","doi":"10.1146/annurev-virology-040323-082822","DOIUrl":"10.1146/annurev-virology-040323-082822","url":null,"abstract":"<p><p>Despite antiretroviral therapy (ART), people living with human immunodeficiency virus (HIV) (PLWH) continue to experience chronic inflammation and immune dysfunction, which drives the persistence of latent HIV and prevalence of clinical comorbidities. Elucidating the mechanisms that lead to suboptimal immunity is necessary for developing therapeutics that improve the quality of life of PLWH. Although previous studies have found associations between gut dysbiosis and immune dysfunction, the cellular/molecular cascades implicated in the manifestation of aberrant immune responses downstream of microbial perturbations in PLWH are incompletely understood. Recent literature has highlighted that two abundant metabolite families, short-chain fatty acids (SCFAs) and bile acids (BAs), play a crucial role in shaping immunity. These metabolites can be produced and/or modified by bacterial species that make up the gut microbiota and may serve as the causal link between changes to the gut microbiome, chronic inflammation, and immune dysfunction in PLWH. In this review, we discuss our current understanding of the role of the microbiome on HIV acquisition and latent HIV persistence despite ART. Further, we describe cellular/molecular cascades downstream of SCFAs and BAs that drive innate or adaptive immune responses responsible for promoting latent HIV persistence in PLWH. This knowledge can be used to advance HIV cure efforts.</p>","PeriodicalId":48761,"journal":{"name":"Annual Review of Virology","volume":null,"pages":null},"PeriodicalIF":11.3,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41136453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-29Epub Date: 2023-04-18DOI: 10.1146/annurev-virology-111821-115754
Danielle E Campbell, Yuhao Li, Harshad Ingle, Megan T Baldridge
The mammalian gastrointestinal tract (GIT) hosts a diverse and highly active microbiota composed of bacteria, eukaryotes, archaea, and viruses. Studies of the GIT microbiota date back more than a century, although modern techniques, including mouse models, sequencing technology, and novel therapeutics in humans, have been foundational to our understanding of the roles of commensal microbes in health and disease. Here, we review the impacts of the GIT microbiota on viral infection, both within the GIT and systemically. GIT-associated microbes and their metabolites alter the course of viral infection through a variety of mechanisms, including direct interactions with virions, alteration of the GIT landscape, and extensive regulation of innate and adaptive immunity. Mechanistic understanding of the full breadth of interactions between the GIT microbiota and the host is still lacking in many ways but will be vital for the development of novel therapeutics for viral and nonviral diseases alike.
{"title":"Impact of the Microbiota on Viral Infections.","authors":"Danielle E Campbell, Yuhao Li, Harshad Ingle, Megan T Baldridge","doi":"10.1146/annurev-virology-111821-115754","DOIUrl":"10.1146/annurev-virology-111821-115754","url":null,"abstract":"<p><p>The mammalian gastrointestinal tract (GIT) hosts a diverse and highly active microbiota composed of bacteria, eukaryotes, archaea, and viruses. Studies of the GIT microbiota date back more than a century, although modern techniques, including mouse models, sequencing technology, and novel therapeutics in humans, have been foundational to our understanding of the roles of commensal microbes in health and disease. Here, we review the impacts of the GIT microbiota on viral infection, both within the GIT and systemically. GIT-associated microbes and their metabolites alter the course of viral infection through a variety of mechanisms, including direct interactions with virions, alteration of the GIT landscape, and extensive regulation of innate and adaptive immunity. Mechanistic understanding of the full breadth of interactions between the GIT microbiota and the host is still lacking in many ways but will be vital for the development of novel therapeutics for viral and nonviral diseases alike.</p>","PeriodicalId":48761,"journal":{"name":"Annual Review of Virology","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10543481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10000932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-29Epub Date: 2023-04-18DOI: 10.1146/annurev-virology-100220-112120
Jimin Yoon, Jessica E Patrick, C Brandon Ogbunugafor, Matthew D Shoulders
Understanding the factors that shape viral evolution is critical for developing effective antiviral strategies, accurately predicting viral evolution, and preventing pandemics. One fundamental determinant of viral evolution is the interplay between viral protein biophysics and the host machineries that regulate protein folding and quality control. Most adaptive mutations in viruses are biophysically deleterious, resulting in a viral protein product with folding defects. In cells, protein folding is assisted by a dynamic system of chaperones and quality control processes known as the proteostasis network. Host proteostasis networks can determine the fates of viral proteins with biophysical defects, either by assisting with folding or by targeting them for degradation. In this review, we discuss and analyze new discoveries revealing that host proteostasis factors can profoundly shape the sequence space accessible to evolving viral proteins. We also discuss the many opportunities for research progress proffered by the proteostasis perspective on viral evolution and adaptation.
{"title":"Viral Evolution Shaped by Host Proteostasis Networks.","authors":"Jimin Yoon, Jessica E Patrick, C Brandon Ogbunugafor, Matthew D Shoulders","doi":"10.1146/annurev-virology-100220-112120","DOIUrl":"10.1146/annurev-virology-100220-112120","url":null,"abstract":"<p><p>Understanding the factors that shape viral evolution is critical for developing effective antiviral strategies, accurately predicting viral evolution, and preventing pandemics. One fundamental determinant of viral evolution is the interplay between viral protein biophysics and the host machineries that regulate protein folding and quality control. Most adaptive mutations in viruses are biophysically deleterious, resulting in a viral protein product with folding defects. In cells, protein folding is assisted by a dynamic system of chaperones and quality control processes known as the proteostasis network. Host proteostasis networks can determine the fates of viral proteins with biophysical defects, either by assisting with folding or by targeting them for degradation. In this review, we discuss and analyze new discoveries revealing that host proteostasis factors can profoundly shape the sequence space accessible to evolving viral proteins. We also discuss the many opportunities for research progress proffered by the proteostasis perspective on viral evolution and adaptation.</p>","PeriodicalId":48761,"journal":{"name":"Annual Review of Virology","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10543606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9412387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-29DOI: 10.1146/annurev-vi-09-071222-100001
Lynn W Enquist, Daniel DiMaio, Terence S Dermody
{"title":"Introduction: Virology in the Headlines.","authors":"Lynn W Enquist, Daniel DiMaio, Terence S Dermody","doi":"10.1146/annurev-vi-09-071222-100001","DOIUrl":"https://doi.org/10.1146/annurev-vi-09-071222-100001","url":null,"abstract":"","PeriodicalId":48761,"journal":{"name":"Annual Review of Virology","volume":null,"pages":null},"PeriodicalIF":11.3,"publicationDate":"2022-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40383119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-29DOI: 10.1146/annurev-virology-091919-064218
David C Baulcombe
Adaptive antiviral immunity in plants is an RNA-based mechanism in which small RNAs derived from both strands of the viral RNA are guides for an Argonaute (AGO) nuclease. The primed AGO specifically targets and silences the viral RNA. In plants this system has diversified to involve mobile small interfering RNAs (siRNAs), an amplification system involving secondary siRNAs and targeting mechanisms involving DNA methylation. Most, if not all, plant viruses encode multifunctional proteins that are suppressors of RNA silencing that may also influence the innate immune system and fine-tune the virus-host interaction. Animal viruses similarly trigger RNA silencing, although it may be masked in differentiated cells by the interferon system and by the action of the virus-encoded suppressor proteins. There is huge potential for RNA silencing to combat viral disease in crops, farm animals, and people, although there are complications associated with the various strategies for siRNA delivery including transgenesis. Alternative approaches could include using breeding or small molecule treatment to enhance the inherent antiviral capacity of infected cells.
{"title":"The Role of Viruses in Identifying and Analyzing RNA Silencing.","authors":"David C Baulcombe","doi":"10.1146/annurev-virology-091919-064218","DOIUrl":"https://doi.org/10.1146/annurev-virology-091919-064218","url":null,"abstract":"<p><p>Adaptive antiviral immunity in plants is an RNA-based mechanism in which small RNAs derived from both strands of the viral RNA are guides for an Argonaute (AGO) nuclease. The primed AGO specifically targets and silences the viral RNA. In plants this system has diversified to involve mobile small interfering RNAs (siRNAs), an amplification system involving secondary siRNAs and targeting mechanisms involving DNA methylation. Most, if not all, plant viruses encode multifunctional proteins that are suppressors of RNA silencing that may also influence the innate immune system and fine-tune the virus-host interaction. Animal viruses similarly trigger RNA silencing, although it may be masked in differentiated cells by the interferon system and by the action of the virus-encoded suppressor proteins. There is huge potential for RNA silencing to combat viral disease in crops, farm animals, and people, although there are complications associated with the various strategies for siRNA delivery including transgenesis. Alternative approaches could include using breeding or small molecule treatment to enhance the inherent antiviral capacity of infected cells.</p>","PeriodicalId":48761,"journal":{"name":"Annual Review of Virology","volume":null,"pages":null},"PeriodicalIF":11.3,"publicationDate":"2022-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10580051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}