{"title":"A Structural Perspective on the Alphavirus Life Cycle.","authors":"Dahai Luo, Yaw Bia Tan, Michelle Cheok Yien Law, Jing Jin","doi":"10.1146/annurev-virology-093022-010359","DOIUrl":"https://doi.org/10.1146/annurev-virology-093022-010359","url":null,"abstract":"<p><p>Alphaviruses are mosquito-borne, enveloped viruses with a positive-sense, single-stranded RNA genome. Alphaviruses enter host cells via receptor-mediated endocytosis, using various cellular surface receptors such as matrix remodeling-associated protein 8 (MXRA8), low-density lipoprotein receptor class A domain-containing 3 (LDLRAD3), and very low-density lipoprotein receptor (VLDLR), which facilitate binding to the viral glycoproteins. Following entry, viral proteins are expressed and nonstructural proteins assemble into replication complexes in host cells, driving RNA synthesis and genome replication. Viral assembly occurs at the plasma membrane, where nascent virions bud from the host cell in a process driven by capsid and spike proteins. Recent combinatorial structural studies have provided detailed molecular insights into various steps of the alphavirus life cycle. These structural insights into the alphavirus life cycle enhance our understanding of viral replication and assembly, with significant implications for antiviral strategies and the development of alphavirus-based vaccine vectors.</p>","PeriodicalId":48761,"journal":{"name":"Annual Review of Virology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144734359","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}
{"title":"CRISPR-Cas in the Cheese Industry.","authors":"Audrey Leprince, Sylvain Moineau","doi":"10.1146/annurev-virology-092623-111016","DOIUrl":"https://doi.org/10.1146/annurev-virology-092623-111016","url":null,"abstract":"<p><p>Bacteria have evolved a wide range of defense systems to combat phage infections. In the cheese industry, lactic acid bacteria (LAB) used for milk fermentation continuously face threats from phages. Therefore, selecting or developing industrial strains with enhanced phage resistance requires a focus on robust defense systems. Among these systems, the clustered regularly interspaced short palindromic repeats (CRISPR) and their CRISPR-associated proteins (Cas) are notably prevalent in LAB. The early characterization of this adaptive immune system was closely tied to the cheese industry, particularly with <i>Streptococcus thermophilus</i> in which CRISPR-Cas systems are ubiquitous and highly active. This review underscores the contributions of <i>S. thermophilus</i> and its virulent phages to our understanding of the function and mechanisms of CRISPR-Cas systems. Additionally, we review the diversity of CRISPR-Cas systems in LAB used in the cheese industry, the counter-defense strategies employed by dairy phages, and the applications of CRISPR-Cas systems within this sector.</p>","PeriodicalId":48761,"journal":{"name":"Annual Review of Virology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144498783","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}
{"title":"Shaping Viral Infection Outcomes via Organelle Remodeling.","authors":"William A Hofstadter, Ileana M Cristea","doi":"10.1146/annurev-virology-092623-094221","DOIUrl":"https://doi.org/10.1146/annurev-virology-092623-094221","url":null,"abstract":"<p><p>Subcellular organelles are dynamic structures that tune their functions in conjunction with changes to their shapes and compositions. Each organelle has distinct structure-function relationships that change in response to diverse stimuli. Such remodeling events further affect organelle-organelle interaction networks facilitated by membrane contact sites, thereby activating rapid intra- and intercellular communication cascades. As viruses rely on repurposing the host cell machinery during infections, organelle remodeling is a fundamental facet and outcome of all viral infections. Some organelle remodeling events are unique to particular viruses, while others are shared by an array of viruses. Here, we review knowledge derived from this expanding yet still underexplored research area of infection-induced organelle remodeling. We focus on the molecular mechanisms used by viruses to temporally control organelle structure-function relationships. We highlight how organelle remodeling can inhibit host defenses or facilitate specific stages of a virus replication cycle, i.e., entry, replication, assembly, and spread.</p>","PeriodicalId":48761,"journal":{"name":"Annual Review of Virology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144486735","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}
{"title":"The Evolution of Virulence: An Ecological Perspective.","authors":"Andrew Dobson","doi":"10.1146/annurev-virology-093022-020712","DOIUrl":"https://doi.org/10.1146/annurev-virology-093022-020712","url":null,"abstract":"<p><p>The evolution of pathogen virulence is a central question in evolutionary epidemiology. This review examines the development of these ideas over the last 75 years from an ecological perspective using a mixture of theoretical and empirical studies. I begin with Fenner's work on myxomatosis, which led to the key concept that trade-offs exist between transmission and virulence in pathogen life histories. I then consider how models of Fenner's study gradually developed into a major area of theoretical epidemiology. The emerging concepts were constantly challenged by new empirical studies that illustrated how virulence may be modified by culling, vaccination, and different forms of heterogeneity within and between species and spatial heterogeneity. The emerging field of phylodynamics has provided multiple new tools to analyze and visualize the evolution of virulence and a much broader perspective on the diversity of viruses and their hosts. I conclude with a brief discussion of possible future directions of study.</p>","PeriodicalId":48761,"journal":{"name":"Annual Review of Virology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477403","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}
{"title":"In Transition: How Influenza Virus Switches from Transcription to Genome Replication.","authors":"Tao Deng, Lei Zhang, Yi Shi, George F Gao","doi":"10.1146/annurev-virology-092623-095030","DOIUrl":"10.1146/annurev-virology-092623-095030","url":null,"abstract":"<p><p>Influenza virus is a segmented, single-stranded, negative-sense RNA virus. Viral genome transcription (to make more viral messenger RNA) and replication (to make more viral genome) of influenza virus are catalyzed by the influenza viral RNA-dependent RNA polymerase (FluPol) in the context of the viral ribonucleoprotein complexes in the nucleus of infected cells. The dynamics of the transcription and replication are tightly regulated throughout the viral life cycle, with a switch from transcription to replication in the later stages of infection being essential for efficient progeny virus production. The mechanism by which the virus achieves the switch has emerged recently through structural and functional studies. Here, we summarize the current hypotheses of the regulatory mechanisms governing the switch. Specifically, we highlight our recent findings showing that the late expression of the viral nonstructural protein NS2, which resulted from a suboptimal splicing site in the NS segment, functions as a molecular timer to mediate the transcription-to-replication switch.</p>","PeriodicalId":48761,"journal":{"name":"Annual Review of Virology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337161","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}
{"title":"Potato Leafroll Virus in the Aphid Holobiont: Interactions Shaping Vector Biology.","authors":"Stephanie E Preising, Michelle Lynn Heck","doi":"10.1146/annurev-virology-092623-103226","DOIUrl":"https://doi.org/10.1146/annurev-virology-092623-103226","url":null,"abstract":"<p><p>The aphid holobiont includes the aphid host and aphid-associated microorganisms, including pathogenic plant viruses. The polerovirus potato leafroll virus (PLRV) is transmitted exclusively by aphids and one of the most economically significant viruses infecting potatoes. In potato plants, PLRV infection results in stunting, leaf rolling, and net necrosis on tubers. PLRV threatens global potato cultivation, especially in regions where vector management options are limited. In this review, we describe the effect of PLRV on the aphid holobiont and highlight studies of the evolutionary and mechanistic ways in which PLRV influences the aphid holobiont during plant infection. We explore ideas to address the pressing need for aphid and PLRV management strategies by targeting interactions within the holobiont. Approaching PLRV-aphid interactions research through the lens of the holobiont allows a systems-level analysis of host, plant, and microbial effects that influence virus transmission. In turn, this knowledge can be leveraged to develop new virus management strategies.</p>","PeriodicalId":48761,"journal":{"name":"Annual Review of Virology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310579","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}
Chase Holdener, Shaowen Jiang, Danica M Sutherland, Kira A Griswold, Terence S Dermody, John S L Parker, Iwijn De Vlaminck
{"title":"Spatial Transcriptomics to Study Virus-Host Interactions.","authors":"Chase Holdener, Shaowen Jiang, Danica M Sutherland, Kira A Griswold, Terence S Dermody, John S L Parker, Iwijn De Vlaminck","doi":"10.1146/annurev-virology-092623-104926","DOIUrl":"https://doi.org/10.1146/annurev-virology-092623-104926","url":null,"abstract":"<p><p>The morbidity and mortality associated with viral diseases in plants, animals, and humans are significant concerns. Understanding how viruses cause disease and identifying the viral and host factors that determine the outcome of infection are essential to develop new antiviral therapeutics and strategies to induce protective immunity. In this review, we focus on the transformative potential of spatial transcriptomics for studies of viral pathogenesis and some of the intricacies of corresponding technologies and how to implement them.</p>","PeriodicalId":48761,"journal":{"name":"Annual Review of Virology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310580","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}
Patricia M B Fernandes, Antonio Alberto R Fernandes, Marlonni Maurastoni, Silas P Rodrigues
{"title":"Lab Legends and Field Phantoms: The Tale of Virus-Resistant Plants.","authors":"Patricia M B Fernandes, Antonio Alberto R Fernandes, Marlonni Maurastoni, Silas P Rodrigues","doi":"10.1146/annurev-virology-092623-101850","DOIUrl":"https://doi.org/10.1146/annurev-virology-092623-101850","url":null,"abstract":"<p><p>Plant viruses present significant challenges to global agriculture, causing crop losses, threatening food security, and imposing economic burdens. Advances in biotechnology have revolutionized strategies to attack these threats, with genetically modified and genome-edited virus-resistant plants, developed using precision tools such as RNA interference and CRISPR/Cas technology, playing pivotal roles. Despite these breakthroughs, fragmented regulatory frameworks and divergent policies across regions including the European Union and the Global South hinder the global adoption of such innovations. Multifaceted approaches, including gene pyramiding, microbiome-based strategies, and pathogen-targeted defenses, show promise for enhancing plant resilience. This review explores the biological, regulatory, and ethical dimensions of deploying virus-resistant crops, emphasizing the need for harmonization of international regulation to maximize biotechnological benefits. By addressing these challenges, biotechnology can advance sustainable agriculture, secure food systems, and mitigate the effect of plant viral diseases.</p>","PeriodicalId":48761,"journal":{"name":"Annual Review of Virology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276302","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}
James McAuliffe, Karolina Bentkowska, Sumana Sanyal
{"title":"Flavivirus Morphogenesis and Its Implications for Pathogenesis.","authors":"James McAuliffe, Karolina Bentkowska, Sumana Sanyal","doi":"10.1146/annurev-virology-092623-110537","DOIUrl":"https://doi.org/10.1146/annurev-virology-092623-110537","url":null,"abstract":"<p><p>Flaviviruses represent major human pathogens transmitted by arthropod vectors, causing significant morbidity and mortality worldwide. Morphogenesis-the assembly and maturation of infectious flavivirus particles-is a complex process that occurs in association with host cell membranes and requires extensive cellular remodeling. This review examines recent advances in our understanding of flavivirus morphogenesis, from the molecular mechanisms driving virion assembly to their implications for viral pathogenesis. We discuss how viral proteins orchestrate the assembly process through interactions with the host cell machinery, particularly focusing on membrane reorganization, lipid metabolism, and post-translational modifications. The production of structurally heterogeneous viral particles is a key feature of flavivirus morphogenesis with important consequences for immune recognition and viral fitness. Understanding these fundamental aspects of the flavivirus life cycle has led to new insights into virus-host interactions and highlights promising targets for therapeutic intervention.</p>","PeriodicalId":48761,"journal":{"name":"Annual Review of Virology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267727","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}
{"title":"Molecular Insights into Noncanonical Influenza Virus Replication and Transcription.","authors":"Michael S Oade, Aartjan J W Te Velthuis","doi":"10.1146/annurev-virology-092623-101331","DOIUrl":"https://doi.org/10.1146/annurev-virology-092623-101331","url":null,"abstract":"<p><p>Influenza A viruses (IAVs) typically cause a mild to moderate respiratory disease, whereas infections with pandemic and highly pathogenic avian IAV strains are frequently associated with high morbidity and death. Various noncanonical or aberrant transcription and replication products have been implicated in the effect of IAV infection on disease outcomes. While early research indicated that all these molecules may be defective, recent findings coupled with analyses of the structure of the IAV RNA polymerase suggest that the production of noncanonical RNAs is not solely driven by errors. Instead, their place in infection may be more nuanced. In this review, we discuss our current understanding of the molecular steps that underlie noncanonical transcription and replication and which molecular mysteries remain.</p>","PeriodicalId":48761,"journal":{"name":"Annual Review of Virology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250446","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}