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  • Everything You Always Wanted to Know About Rabies Virus (But Were Afraid to Ask).
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Benjamin M Davis,Glenn F Rall,Matthias J Schnell

    The cultural impact of rabies, the fatal neurological disease caused by infection with rabies virus, registers throughout recorded history. Although rabies has been the subject of large-scale public health interventions, chiefly through vaccination efforts, the disease continues to take the lives of about 40,000-70,000 people per year, roughly 40% of whom are children. Most of these deaths occur in resource-poor countries, where lack of infrastructure prevents timely reporting and postexposure prophylaxis and the ubiquity of domestic and wild animal hosts makes eradication unlikely. Moreover, although the disease is rarer than other human infections such as influenza, the prognosis following a bite from a rabid animal is poor: There is currently no effective treatment that will save the life of a symptomatic rabies patient. This review focuses on the major unanswered research questions related to rabies virus pathogenesis, especially those connecting the disease progression of rabies with the complex dysfunction caused by the virus in infected cells. The recent applications of cutting-edge research strategies to this question are described in detail.

    更新日期:2019-11-01
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  • Introduction.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2019-10-01
    Lynn W Enquist,Terence S Dermody,Daniel DiMaio

    更新日期:2019-11-01
  • Pathophysiological Consequences of Calcium-Conducting Viroporins.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Joseph M Hyser,Mary K Estes

    Eukaryotic cells have evolved a myriad of ion channels, transporters, and pumps to maintain and regulate transmembrane ion gradients. As intracellular parasites, viruses also have evolved ion channel proteins, called viroporins, which disrupt normal ionic homeostasis to promote viral replication and pathogenesis. The first viral ion channel (influenza M2 protein) was confirmed only 23 years ago, and since then studies on M2 and many other viroporins have shown they serve critical functions in virus entry, replication, morphogenesis, and immune evasion. As new candidate viroporins and viroporin-mediated functions are being discovered, we review the experimental criteria for viroporin identification and characterization to facilitate consistency within this field of research. Then we review recent studies on how the few Ca(2+)-conducting viroporins exploit host signaling pathways, including store-operated Ca(2+) entry, autophagy, and inflammasome activation. These viroporin-induced aberrant Ca(2+) signals cause pathophysiological changes resulting in diarrhea, vomiting, and proinflammatory diseases, making both the viroporin and host Ca(2+) signaling pathways potential therapeutic targets for antiviral drugs.

    更新日期:2019-11-01
  • Introduction.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2018-09-29
    Lynn W Enquist,Terence S Dermody,Daniel DiMaio

    更新日期:2019-11-01
  • Reductio ad Intellectum.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2018-09-29
    Daniel DiMaio,Terence S Dermody,Lynn W Enquist

    更新日期:2019-11-01
  • Innate and Adaptive Immune Regulation During Chronic Viral Infections.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Elina I Zuniga,Monica Macal,Gavin M Lewis,James A Harker

    Chronic viral infections represent a unique challenge to the infected host. Persistently replicating viruses outcompete or subvert the initial antiviral response, allowing the establishment of chronic infections that result in continuous stimulation of both the innate and adaptive immune compartments. This causes a profound reprogramming of the host immune system, including attenuation and persistent low levels of type I interferons, progressive loss (or exhaustion) of CD8(+) T cell functions, and specialization of CD4(+) T cells to produce interleukin-21 and promote antibody-mediated immunity and immune regulation. Epigenetic, transcriptional, posttranscriptional, and metabolic changes underlie this adaptation or recalibration of immune cells to the emerging new environment in order to strike an often imperfect balance between the host and the infectious pathogen. In this review we discuss the common immunological hallmarks observed across a range of different persistently replicating viruses and host species, the underlying molecular mechanisms, and the biological and clinical implications.

    更新日期:2019-11-01
  • The Good That Viruses Do.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2017-09-30
    Mario Mietzsch,Mavis Agbandje-McKenna

    更新日期:2019-11-01
  • Introduction.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2017-09-30
    Lynn W Enquist,Terence S Dermody,Daniel DiMaio

    更新日期:2019-11-01
  • Introduction.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2015-11-09
    Lynn W Enquist,Terence S Dermody,Daniel DiMaio

    更新日期:2019-11-01
  • Introduction.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-09-29
    Lynn W Enquist,Terence S Dermody,Daniel DiMaio

    更新日期:2019-11-01
  • A Diversified Portfolio.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-09-29
    Michael M Goodin,Graham F Hatfull,Harmit S Malik

    更新日期:2019-11-01
  • Welcome to the Annual Review of Virology.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2014-11-03
    Lynn W Enquist,Terence S Dermody,Daniel DiMaio

    更新日期:2019-11-01
  • Genetics in Virology Research.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2015-11-09
    Terence S Dermody,Julie K Pfeiffer

    更新日期:2019-11-01
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  • IFITM-Family Proteins: The Cell's First Line of Antiviral Defense.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2015-01-20
    Charles C Bailey,Guocai Zhong,I-Chueh Huang,Michael Farzan

    Animal cells use a wide variety of mechanisms to slow or prevent replication of viruses. These mechanisms are usually mediated by antiviral proteins whose expression and activities can be constitutive but are frequently amplified by interferon induction. Among these interferon-stimulated proteins, members of the IFITM (interferon-induced transmembrane) family are unique because they prevent infection before a virus can traverse the lipid bilayer of the cell. At least three human IFITM proteins-IFITM1, IFITM2, and IFITM3-have antiviral activities. These activities limit infection in cultured cells by many viruses, including dengue virus, Ebola virus, influenza A virus, severe acute respiratory syndrome coronavirus, and West Nile virus. Murine Ifitm3 controls influenza A virus infection in vivo, and polymorphisms in human IFITM3 correlate with the severity of both seasonal and highly pathogenic avian influenza virus. Here we review the discovery and characterization of the IFITM proteins, describe the spectrum of their antiviral activities, and discuss potential mechanisms underlying these effects.

    更新日期:2019-11-01
  • Bacteriophage Therapy: Advances in Formulation Strategies and Human Clinical Trials.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Dieter Vandenheuvel,Rob Lavigne,Harald Brüssow

    Recently, a number of phage therapy phase I and II safety trials have been concluded, showing no notable safety concerns associated with the use of phage. Though hurdles for efficient treatment remain, these trials hold promise for future phase III clinical trials. Interestingly, most phage formulations used in these clinical trials are straightforward phage suspensions, and not much research has focused on the processing of phage cocktails in specific pharmaceutical dosage forms. Additional research on formulation strategies and the stability of phage-based drugs will be of key importance, especially with phage therapy advancing toward phase III clinical trials.

    更新日期:2019-11-01
  • Viruses in Rodent Colonies: Lessons Learned from Murine Noroviruses.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Stephanie M Karst,Christiane E Wobus

    Noroviruses (NoVs) are highly prevalent, positive-sense RNA viruses that infect a range of mammals, including humans and mice. Murine noroviruses (MuNoVs) are the most prevalent pathogens in biomedical research colonies, and they have been used extensively as a model system for human noroviruses (HuNoVs). Despite recent successes in culturing HuNoVs in the laboratory and a small animal host, studies of human viruses have inherent limitations. Thus, owing to its versatility, the MuNoV system-with its native host, reverse genetics, and cell culture systems-will continue to provide important insights into NoV and enteric virus biology. In the current review, we summarize recent findings from MuNoVs that increase our understanding of enteric virus pathogenesis and highlight similarities between human and murine NoVs that underscore the value of MuNoVs to inform studies of HuNoV biology. We also discuss the potential of endemic MuNoV infections to impact other disease models.

    更新日期:2019-11-01
  • No Love Lost Between Viruses and Interferons.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Volker Fensterl,Saurabh Chattopadhyay,Ganes C Sen

    The interferon system protects mammals against virus infections. There are several types of interferons, which are characterized by their ability to inhibit virus replication and resultant pathogenesis by triggering both innate and cell-mediated immune responses. Virus infection is sensed by a variety of cellular pattern-recognition receptors and triggers the synthesis of interferons, which are secreted by the infected cells. In uninfected cells, cell surface receptors recognize the secreted interferons and activate intracellular signaling pathways that induce the expression of interferon-stimulated genes; the proteins encoded by these genes inhibit different stages of virus replication. To avoid extinction, almost all viruses have evolved mechanisms to defend themselves against the interferon system. Consequently, a dynamic equilibrium of survival is established between the virus and its host, an equilibrium that can be shifted to the host's favor by the use of exogenous interferon as a therapeutic antiviral agent.

    更新日期:2019-11-01
  • Virus-Host Interactions: From Unbiased Genetic Screens to Function.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Holly Ramage,Sara Cherry

    Deciphering the many interactions that occur between a virus and host cell over the course of infection is paramount to understanding mechanisms of pathogenesis and to the future development of antiviral therapies. Over the past decade, researchers have started to understand these complicated relationships through the development of methodologies, including advances in RNA interference, proteomics, and the development of genetic tools such as haploid cell lines, allowing high-throughput screening to identify critical contact points between virus and host. These advances have produced a wealth of data regarding host factors hijacked by viruses to promote infection, as well as antiviral factors responsible for subverting viral infection. This review highlights findings from virus-host screens and discusses our thoughts on the direction of screening strategies moving forward.

    更新日期:2019-11-01
  • Virus-Based Nanoparticles as Versatile Nanomachines.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Kristopher J Koudelka,Andrzej S Pitek,Marianne Manchester,Nicole F Steinmetz

    Nanoscale engineering is revolutionizing the way we prevent, detect, and treat diseases. Viruses have played a special role in these developments because they can function as prefabricated nanoscaffolds that have unique properties and are easily modified. The interiors of virus particles can encapsulate and protect sensitive compounds, while the exteriors can be altered to display large and small molecules in precisely defined arrays. These properties of viruses, along with their innate biocompatibility, have led to their development as actively targeted drug delivery systems that expand on and improve current pharmaceutical options. Viruses are naturally immunogenic, and antigens displayed on their surface have been used to create vaccines against pathogens and to break self-tolerance to initiate an immune response to dysfunctional proteins. Densely and specifically aligned imaging agents on viruses have allowed for high-resolution and noninvasive visualization tools to detect and treat diseases earlier than previously possible. These and future applications of viruses have created an exciting new field within the disciplines of both nanotechnology and medicine.

    更新日期:2019-11-01
  • Parvovirus Family Conundrum: What Makes a Killer?
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Shweta Kailasan,Mavis Agbandje-McKenna,Colin R Parrish

    Parvoviruses infect a wide variety of hosts, and their ancestors appear to have emerged tens to hundreds of millions of years ago and to have spread widely ever since. The diversity of parvoviruses is therefore extensive, and although they all appear to descend from a common ancestor and share common structures in their capsid and nonstructural proteins, there is often low homology at the DNA or protein level. The diversity of these viruses is also seen in the widely differing impacts they have on their hosts, which range from severe and even lethal disease to subclinical or nonpathogenic infections. In the past few years, deep sequencing of DNA samples from animals has shown just how widespread the parvoviruses are in nature, but most of the newly discovered viruses have not yet been associated with any disease. However, variants of some parvoviruses have altered their host ranges to create new epidemic or pandemic viruses. Here, we examine the properties of parvoviruses and their interactions with their hosts that are associated with these disparate pathogenic outcomes.

    更新日期:2019-11-01
  • Mechanisms of DNA Packaging by Large Double-Stranded DNA Viruses.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Venigalla B Rao,Michael Feiss

    Translocation of viral double-stranded DNA (dsDNA) into the icosahedral prohead shell is catalyzed by TerL, a motor protein that has ATPase, endonuclease, and translocase activities. TerL, following endonucleolytic cleavage of immature viral DNA concatemer recognized by TerS, assembles into a pentameric ring motor on the prohead's portal vertex and uses ATP hydrolysis energy for DNA translocation. TerL's N-terminal ATPase is connected by a hinge to the C-terminal endonuclease. Inchworm models propose that modest domain motions accompanying ATP hydrolysis are amplified, through changes in electrostatic interactions, into larger movements of the C-terminal domain bound to DNA. In phage ϕ29, four of the five TerL subunits sequentially hydrolyze ATP, each powering translocation of 2.5 bp. After one viral genome is encapsidated, the internal pressure signals termination of packaging and ejection of the motor. Current focus is on the structures of packaging complexes and the dynamics of TerL during DNA packaging, endonuclease regulation, and motor mechanics.

    更新日期:2019-11-01
  • Novel Functions of the Human Papillomavirus E6 Oncoproteins.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Nicholas A Wallace,Denise A Galloway

    Human papillomaviruses (HPVs) infect the epidermis as well as mucous membranes of humans. They are the causative agents of anogenital tract and some oropharyngeal cancers. Infections begin in the basal epithelia, where the viral genome replicates slowly along with its host cell. As infected cells begin to differentiate and progress toward the periphery, the virus drives proliferation in cells that would otherwise be quiescent. To uncouple differentiation from continued cellular propagation, HPVs express two oncoproteins, HPV E6 and E7. This review focuses on high-risk α-HPV E6, which in addition to supporting viral replication has transforming properties. HPV E6 promotes p53 degradation and activates telomerase, but the multifaceted oncoprotein has numerous other functions that are highlighted here.

    更新日期:2019-11-01
  • Modulation of the Translational Landscape During Herpesvirus Infection.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Britt A Glaunsinger

    Herpesviral mRNAs are produced and translated by cellular machinery, rendering them susceptible to the network of regulatory events that impact translation. In response, these viruses have evolved to infiltrate and hijack translational control pathways as well as to integrate specialized host translation strategies into their own repertoire. They are robust systems to dissect mechanisms of mammalian translational regulation and continue to offer insight into cis-acting mRNA features that impact assembly and activity of the translation apparatus. Here, I discuss recent advances revealing the extent to which the three herpesvirus subfamilies regulate both host and viral translation, thereby dramatically impacting the landscape of protein synthesis in infected cells.

    更新日期:2019-11-01
  • Continuous and Discontinuous RNA Synthesis in Coronaviruses.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Isabel Sola,Fernando Almazán,Sonia Zúñiga,Luis Enjuanes

    Replication of the coronavirus genome requires continuous RNA synthesis, whereas transcription is a discontinuous process unique among RNA viruses. Transcription includes a template switch during the synthesis of subgenomic negative-strand RNAs to add a copy of the leader sequence. Coronavirus transcription is regulated by multiple factors, including the extent of base-pairing between transcription-regulating sequences of positive and negative polarity, viral and cell protein-RNA binding, and high-order RNA-RNA interactions. Coronavirus RNA synthesis is performed by a replication-transcription complex that includes viral and cell proteins that recognize cis-acting RNA elements mainly located in the highly structured 5' and 3' untranslated regions. In addition to many viral nonstructural proteins, the presence of cell nuclear proteins and the viral nucleocapsid protein increases virus amplification efficacy. Coronavirus RNA synthesis is connected with the formation of double-membrane vesicles and convoluted membranes. Coronaviruses encode proofreading machinery, unique in the RNA virus world, to ensure the maintenance of their large genome size.

    更新日期:2019-11-01
  • Ribosome Profiling as a Tool to Decipher Viral Complexity.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Noam Stern-Ginossar,Nicholas T Ingolia

    Viral genomes harbor a variety of unusual translational phenomena that allow them to pack coding information more densely and evade host restriction mechanisms imposed by the cellular translational apparatus. Annotating translated sequences within these genomes thus poses particular challenges, but identifying the full complement of proteins encoded by a virus is critical for understanding its life cycle and defining the epitopes it presents for immune surveillance. Ribosome profiling is an emerging technique for global analysis of translation that offers direct and experimental annotation of viral genomes. Ribosome profiling has been applied to two herpesvirus genomes, those of human cytomegalovirus and Kaposi's sarcoma-associated herpesvirus, revealing translated sequences within presumptive long noncoding RNAs and identifying other micropeptides. Synthesis of these proteins has been confirmed by mass spectrometry and by identifying T cell responses following infection. Ribosome profiling in other viruses will likely expand further our understanding of viral gene regulation and the proteome.

    更新日期:2019-11-01
  • Retroviral Integrase: Then and Now.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Mark D Andrake,Anna Marie Skalka

    The retroviral integrases are virally encoded, specialized recombinases that catalyze the insertion of viral DNA into the host cell's DNA, a process that is essential for virus propagation. We have learned a great deal since the existence of an integrated form of retroviral DNA (the provirus) was first proposed by Howard Temin in 1964. Initial studies focused on the genetics and biochemistry of avian and murine virus DNA integration, but the pace of discovery increased substantially with advances in technology, and an influx of investigators focused on the human immunodeficiency virus. We begin with a brief account of the scientific landscape in which some of the earliest discoveries were made, and summarize research that led to our current understanding of the biochemistry of integration. A more detailed account of recent analyses of integrase structure follows, as they have provided valuable insights into enzyme function and raised important new questions.

    更新日期:2019-11-01
  • Flaviviridae Replication Organelles: Oh, What a Tangled Web We Weave.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    David Paul,Ralf Bartenschlager

    Replication of positive-strand RNA viruses occurs in tight association with reorganized host cell membranes. In a concerted fashion, viral and cellular factors generate distinct organelle-like structures, designated viral replication factories. These virus-induced compartments promote highly efficient genome replication, allow spatiotemporal coordination of the different steps of the viral replication cycle, and protect viral RNA from the hostile cytoplasmic environment. The combined use of ultrastructural and functional studies has greatly increased our understanding of the architecture and biogenesis of viral replication factories. Here, we review common concepts and distinct differences in replication organelle morphology and biogenesis within the Flaviviridae family, exemplified by dengue virus and hepatitis C virus. We discuss recent progress made in our understanding of the complex interplay between viral determinants and subverted cellular membrane homeostasis in biogenesis and maintenance of replication factories of this virus family.

    更新日期:2019-11-01
  • Hunting Viral Receptors Using Haploid Cells.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Sirika Pillay,Jan E Carette

    Viruses have evolved intricate mechanisms to gain entry into the host cell. Identification of host proteins that serve as viral receptors has enabled insights into virus particle internalization, host and tissue tropism, and viral pathogenesis. In this review we discuss the most commonly employed methods for virus receptor discovery, specifically highlighting the use of forward genetic screens in human haploid cells. The ability to generate true knockout alleles at high saturation provides a sensitive means to study virus-host interactions. To illustrate the power of such haploid genetic screens, we highlight the discovery of the lysosomal proteins NPC1 and LAMP1 as intracellular receptors for Ebola virus and Lassa virus, respectively. From these studies emerges the notion that receptor usage by these viruses is highly dynamic, involving a programmed switch from cell surface receptor to intracellular receptor. Broad application of genetic knockout approaches will chart functional landscapes of receptors and endocytic pathways hijacked by viruses.

    更新日期:2019-11-01
  • Deep Recombination: RNA and ssDNA Virus Genes in DNA Virus and Host Genomes.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Kenneth M Stedman

    Viruses are notorious for rapidly exchanging genetic information between close relatives and with the host cells they infect. This exchange has profound effects on the nature and rapidity of virus and host evolution. Recombination between dsDNA viruses is common, as is genetic exchange between dsDNA viruses or retroviruses and host genomes. Recombination between RNA virus genomes is also well known. In contrast, genetic exchange across viral kingdoms, for instance between nonretroviral RNA viruses or ssDNA viruses and host genomes or between RNA and DNA viruses, was previously thought to be practically nonexistent. However, there is now growing evidence for both RNA and ssDNA viruses recombining with host dsDNA genomes and, more surprisingly, RNA virus genes recombining with ssDNA virus genomes. Mechanisms are still unclear, but this deep recombination greatly expands the breadth of virus evolution and confounds virus taxonomy.

    更新日期:2019-11-01
  • The Phage-Inducible Chromosomal Islands: A Family of Highly Evolved Molecular Parasites.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    José R Penadés,Gail E Christie

    The phage-inducible chromosomal islands (PICIs) are a family of highly mobile genetic elements that contribute substantively to horizontal gene transfer, host adaptation, and virulence. Initially identified in Staphylococcus aureus, these elements are now thought to occur widely in gram-positive bacteria. They are molecular parasites that exploit certain temperate phages as helpers, using a variety of elegant strategies to manipulate the phage life cycle and promote their own spread, both intra- and intergenerically. At the same time, these PICI-encoded mechanisms severely interfere with helper phage reproduction, thereby enhancing survival of the bacterial population. In this review we discuss the genetics and the life cycle of these elements, with special emphasis on how they interact and interfere with the helper phage machinery for their own benefit. We also analyze the role that these elements play in driving bacterial and viral evolution.

    更新日期:2019-11-01
  • Matters of Size: Genetic Bottlenecks in Virus Infection and Their Potential Impact on Evolution.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Mark P Zwart,Santiago F Elena

    For virus infections of multicellular hosts, narrow genetic bottlenecks during transmission and within-host spread appear to be widespread. These bottlenecks will affect the maintenance of genetic variation in a virus population and the prevalence of mixed-strain infections, thereby ultimately determining the strength with which different random forces act during evolution. Here we consider different approaches for estimating bottleneck sizes and weigh their merits. We then review quantitative estimates of bottleneck size during cellular infection, within-host spread, horizontal transmission, and finally vertical transmission. In most cases we find that bottlenecks do regularly occur, although in many cases they appear to be virion-concentration dependent. Finally, we consider the evolutionary implications of genetic bottlenecks during virus infection. Although on average strong bottlenecks will lead to declines in fitness, we consider a number of scenarios in which bottlenecks could also be advantageous for viruses.

    更新日期:2019-11-01
  • Endogenous Retroviruses in the Genomics Era.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Welkin E Johnson

    Endogenous retroviruses comprise millions of discrete genetic loci distributed within the genomes of extant vertebrates. These sequences, which are clearly related to exogenous retroviruses, represent retroviral infections of the deep past, and their abundance suggests that retroviruses were a near-constant presence throughout the evolutionary history of modern vertebrates. Endogenous retroviruses contribute in myriad ways to the evolution of host genomes, as mutagens and as sources of genetic novelty (both coding and regulatory) to be acted upon by the twin engines of random genetic drift and natural selection. Importantly, the richness and complexity of endogenous retrovirus data can be used to understand how viruses spread and adapt on evolutionary timescales by combining population genetics and evolutionary theory with a detailed understanding of retrovirus biology (gleaned from the study of extant retroviruses). In addition to revealing the impact of viruses on organismal evolution, such studies can help us better understand, by looking back in time, how life-history traits, as well as ecological and geological events, influence the movement of viruses within and between populations.

    更新日期:2019-11-01
  • Koala Retroviruses: Evolution and Disease Dynamics.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Wenqin Xu,Maribeth V Eiden

    A retroviral etiology for malignant neoplasias in koalas has long been suspected. Evidence for retroviral involvement was bolstered in 2000 by the isolation of a koala retrovirus (KoRV), now termed KoRV-A. KoRV-A is an endogenous retrovirus-a retrovirus that infects germ cells-a feature that makes it a permanent resident of the koala genome. KoRV-A lacks the genetic diversity of an exogenous retrovirus, a quality associated with the ability of a retrovirus to cause neoplasias. In 2013, a second KoRV isolate, KoRV-B, was obtained from koalas with lymphomas in the Los Angeles Zoo. Unlike KoRV-A, which is present in the genomes of all koalas in the United States, KoRV-B is restricted in its distribution and is associated with host pathology (neoplastic disease). Here, our current understanding of the evolution of endogenous and exogenous KoRVs, and the relationship between them, is reviewed to build a perspective on the future impact of these viruses on koala sustainability.

    更新日期:2019-11-01
  • Coronavirus Host Range Expansion and Middle East Respiratory Syndrome Coronavirus Emergence: Biochemical Mechanisms and Evolutionary Perspectives.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Kayla M Peck,Christina L Burch,Mark T Heise,Ralph S Baric

    Coronaviruses have frequently expanded their host range in recent history, with two events resulting in severe disease outbreaks in human populations. Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2003 in Southeast Asia and rapidly spread around the world before it was controlled by public health intervention strategies. The 2012 Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak represents another prime example of virus emergence from a zoonotic reservoir. Here, we review the current knowledge of coronavirus cross-species transmission, with particular focus on MERS-CoV. MERS-CoV is still circulating in the human population, and the mechanisms governing its cross-species transmission have been only partially elucidated, highlighting a need for further investigation. We discuss biochemical determinants mediating MERS-CoV host cell permissivity, including virus spike interactions with the MERS-CoV cell surface receptor dipeptidyl peptidase 4 (DPP4), and evolutionary mechanisms that may facilitate host range expansion, including recombination, mutator alleles, and mutational robustness. Understanding these mechanisms can help us better recognize the threat of emergence for currently circulating zoonotic strains.

    更新日期:2019-11-01
  • Role of the Insect Supervectors Bemisia tabaci and Frankliniella occidentalis in the Emergence and Global Spread of Plant Viruses.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Robert L Gilbertson,Ozgur Batuman,Craig G Webster,Scott Adkins

    Emergence of insect-transmitted plant viruses over the past 10-20 years has been disproportionately driven by two so-called supervectors: the whitefly, Bemisia tabaci, and the Western flower thrips, Frankliniella occidentalis. High rates of reproduction and dispersal, extreme polyphagy, and development of insecticide resistance, together with human activities, have made these insects global pests. These supervectors transmit a diversity of plant viruses by different mechanisms and mediate virus emergence through local evolution, host shifts, mixed infections, and global spread. Associated virus evolution involves reassortment, recombination, and component capture. Emergence of B. tabaci-transmitted geminiviruses (begomoviruses), ipomoviruses, and torradoviruses has led to global disease outbreaks as well as multiple paradigm shifts. Similarly, F. occidentalis has mediated tospovirus host shifts and global dissemination and the emergence of pollen-transmitted ilarviruses. The plant virus-supervector interaction offers exciting opportunities for basic research and global implementation of generalized disease management strategies to reduce economic and environmental impacts.

    更新日期:2019-11-01
  • Biogeography of Viruses in the Sea.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Cheryl-Emiliane T Chow,Curtis A Suttle

    Viral ecology is a rapidly progressing area of research, as molecular methods have improved significantly for targeted research on specific populations and whole communities. To interpret and synthesize global viral diversity and distribution, it is feasible to assess whether macroecology concepts can apply to marine viruses. We review how viral and host life history and physical properties can influence viral distribution in light of biogeography and metacommunity ecology paradigms. We highlight analytical approaches that can be applied to emerging global data sets and meta-analyses to identify individual taxa with global influence and drivers of emergent properties that influence microbial community structure by drawing on examples across the spectrum of viral taxa, from RNA to ssDNA and dsDNA viruses.

    更新日期:2019-11-01
  • The Legacy of Nat Sternberg: The Genesis of Cre-lox Technology.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Michael Yarmolinsky,Ronald Hoess

    Cre-lox of bacteriophage P1 has become one of the most widely used tools for genetic engineering in eukaryotes. The origins of this tool date to more than 30 years ago when Nat L. Sternberg discovered the recombinase, Cre, and its specific locus of crossover, lox, while studying the maintenance of bacteriophage P1 as a stable plasmid. Recombinations mediated by Cre assist in cyclization of the DNA of infecting phage and in resolution of prophage multimers created by generalized recombination. Early in vitro work demonstrated that, although it shares similarities with the well-characterized bacteriophage λ integration, Cre-lox is in many ways far simpler in its requirements for carrying out recombination. These features would prove critical for its development as a powerful and versatile tool in genetic engineering. We review the history of the discovery and characterization of Cre-lox and touch upon the present direction of Cre-lox research.

    更新日期:2019-11-01
  • The Maturation of a Scientist: An Autobiography.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2016-03-10
    Bernard Roizman

    I was shaped by World War II, years of near starvation as a war refugee, postwar chaos, life in several countries, and relative affluence in later life. The truth is that as I was growing up I wanted to be a writer. My aspirations came to an end when, in order to speed up my graduation from college, I took courses in microbiology. It was my second love at first sight-that of my wife preceded it. I view science as an opportunity to discover the designs in the mosaics of life. What initiates my search of discovery is an observation that makes no sense unless there exists a novel design. Once the design is revealed there is little interest in filling all the gaps. I was fortunate to understand that what lasts are not the scientific reports but rather the generations of scientists whose education I may have influenced.

    更新日期:2019-11-01
  • Viruses and the DNA Damage Response: Activation and Antagonism.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2014-11-03
    Micah A Luftig

    Viruses must interact with their hosts in order to replicate; these interactions often provoke the evolutionarily conserved response to DNA damage, known as the DNA damage response (DDR). The DDR can be activated by incoming viral DNA, during the integration of retroviruses, or in response to the aberrant DNA structures generated upon replication of DNA viruses. Furthermore, DNA and RNA viral proteins can induce the DDR by promoting inappropriate S phase entry, by modifying cellular DDR factors directly, or by unintentionally targeting host DNA. The DDR may be antiviral, although viruses often require proximal DDR activation of repair and recombination factors to facilitate replication as well as downstream DDR signaling suppression to ensure cell survival. An unintended consequence of DDR attenuation during infection is the long-term survival and proliferation of precancerous cells. Therefore, the molecular basis for DDR activation and attenuation by viruses remains an important area of study that will likely provide key insights into how viruses have evolved with their hosts.

    更新日期:2019-11-01
  • The Impact of Mass Spectrometry-Based Proteomics on Fundamental Discoveries in Virology.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2014-11-03
    Todd M Greco,Benjamin A Diner,Ileana M Cristea

    In recent years, mass spectrometry has emerged as a core component of fundamental discoveries in virology. As a consequence of their coevolution, viruses and host cells have established complex, dynamic interactions that function either in promoting virus replication and dissemination or in host defense against invading pathogens. Thus, viral infection triggers an impressive range of proteome changes. Alterations in protein abundances, interactions, posttranslational modifications, subcellular localizations, and secretion are temporally regulated during the progression of an infection. Consequently, understanding viral infection at the molecular level requires versatile approaches that afford both breadth and depth of analysis. Mass spectrometry is uniquely positioned to bridge this experimental dichotomy. Its application to both unbiased systems analyses and targeted, hypothesis-driven studies has accelerated discoveries in viral pathogenesis and host defense. Here, we review the contributions of mass spectrometry-based proteomic approaches to understanding viral morphogenesis, replication, and assembly and to characterizing host responses to infection.

    更新日期:2019-11-01
  • In Vitro Assembly of Retroviruses.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2014-11-03
    Di L Bush,Volker M Vogt

    Assembly, part of the late stages of the retroviral life cycle, begins when the structural polyprotein Gag associates with viral genomic RNA. Ultimately, more than a thousand Gag molecules form a spherical immature virion. Maturation takes place soon after or concomitantly with virus budding and is initiated as Gag is cleaved by the retroviral protease into its constituent protein domains. The immature core is thought to disassemble and the liberated CA proteins to reassemble into a morphologically distinct mature capsid. In vitro assembly with derivatives of Gag and CA has been used to study retroviruses for over two decades. In this review, we examine the discovery and development of three major model systems [human immunodeficiency virus type 1 (HIV-1), Rous sarcoma virus (RSV), and Mason-Pfizer monkey virus (MPMV)] and discuss structural features and aspects of the retroviral assembly pathway that have been uncovered using in vitro assembly. We also put forward two major unresolved questions in the field and propose future avenues of research.

    更新日期:2019-11-01
  • Naked Viruses That Aren't Always Naked: Quasi-Enveloped Agents of Acute Hepatitis.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2014-11-03
    Zongdi Feng,Asuka Hirai-Yuki,Kevin L McKnight,Stanley M Lemon

    Historically, viruses were considered to be either enveloped or nonenveloped. However, recent work on hepatitis A virus and hepatitis E virus challenges this long-held tenet. Whereas these human pathogens are shed in feces as naked nonenveloped virions, recent studies indicate that both circulate in the blood completely masked in membranes during acute infection. These membrane-wrapped virions are as infectious as their naked counterparts, although they do not express a virally encoded protein on their surface, thus distinguishing them from conventional enveloped viruses. The absence of a viral fusion protein implies that these quasi-enveloped virions have unique mechanisms for entry into cells. Like true enveloped viruses, however, these phylogenetically distinct viruses usurp components of the host ESCRT system to hijack host cell membranes and noncytolytically exit infected cells. The membrane protects these viruses from neutralizing antibodies, facilitating dissemination within the host, whereas nonenveloped virions shed in feces are stable in the environment, allowing for epidemic transmission.

    更新日期:2019-11-01
  • Parvoviruses: Small Does Not Mean Simple.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2014-11-03
    Susan F Cotmore,Peter Tattersall

    Parvoviruses are small, rugged, nonenveloped protein particles containing a linear, nonpermuted, single-stranded DNA genome of ∼5 kb. Their limited coding potential requires optimal adaptation to the environment of particular host cells, where entry is mediated by a variable program of capsid dynamics, ultimately leading to genome ejection from intact particles within the host nucleus. Genomes are amplified by a continuous unidirectional strand-displacement mechanism, a linear adaptation of rolling circle replication that relies on the repeated folding and unfolding of small hairpin telomeres to reorient the advancing fork. Progeny genomes are propelled by the viral helicase into the preformed capsid via a pore at one of its icosahedral fivefold axes. Here we explore how the fine-tuning of this unique replication system and the mechanics that regulate opening and closing of the capsid fivefold portals have evolved in different viral lineages to create a remarkably complex spectrum of phenotypes.

    更新日期:2019-11-01
  • Live Cell Imaging of Retroviral Entry.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2014-11-03
    Amy E Hulme,Thomas J Hope

    Cellular entry of retroviruses is the first critical stage of retroviral replication. Live cell imaging has been utilized to visualize the dynamics, localization, and kinetics of the viral fusion process. Here, we review the different methodologies used for live cell imaging and how the use of these techniques has better elucidated the viral entry process of avian sarcoma and leukosis virus (ASLV) and human immunodeficiency virus type 1 (HIV-1) as well as cell-to-cell transmission of retroviruses. Although some controversies remain, further development of these techniques will provide new insights into the process and dynamics of retroviral fusion in vivo.

    更新日期:2019-11-01
  • Three-Dimensional Imaging of Viral Infections.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2014-11-03
    Cristina Risco,Isabel Fernández de Castro,Laura Sanz-Sánchez,Kedar Narayan,Giovanna Grandinetti,Sriram Subramaniam

    Three-dimensional (3D) imaging technologies are beginning to have significant impact in the field of virology, as they are helping us understand how viruses take control of cells. In this article we review several methodologies for 3D imaging of cells and show how these technologies are contributing to the study of viral infections and the characterization of specialized structures formed in virus-infected cells. We include 3D reconstruction by transmission electron microscopy (TEM) using serial sections, electron tomography, and focused ion beam scanning electron microscopy (FIB-SEM). We summarize from these methods selected contributions to our understanding of viral entry, replication, morphogenesis, egress and propagation, and changes in the spatial architecture of virus-infected cells. In combination with live-cell imaging, correlative microscopy, and new techniques for molecular mapping in situ, the availability of these methods for 3D imaging is expected to provide deeper insights into understanding the structural and dynamic aspects of viral infection.

    更新日期:2019-11-01
  • AAV-Mediated Gene Therapy for Research and Therapeutic Purposes.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2014-11-03
    R Jude Samulski,Nicholas Muzyczka

    Adeno-associated virus (AAV) is a small, nonenveloped virus that was adapted 30 years ago for use as a gene transfer vehicle. It is capable of transducing a wide range of species and tissues in vivo with no evidence of toxicity, and it generates relatively mild innate and adaptive immune responses. We review the basic biology of AAV, the history of progress in AAV vector technology, and some of the clinical and research applications where AAV has shown success.

    更新日期:2019-11-01
  • Archaeal Viruses: Diversity, Replication, and Structure.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2014-11-03
    Nikki Dellas,Jamie C Snyder,Benjamin Bolduc,Mark J Young

    The Archaea-and their viruses-remain the most enigmatic of life's three domains. Once thought to inhabit only extreme environments, archaea are now known to inhabit diverse environments. Even though the first archaeal virus was described over 40 years ago, only 117 archaeal viruses have been discovered to date. Despite this small number, these viruses have painted a portrait of enormous morphological and genetic diversity. For example, research centered around the various steps of the archaeal virus life cycle has led to the discovery of unique mechanisms employed by archaeal viruses during replication, maturation, and virion release. In many instances, archaeal virus proteins display very low levels of sequence homology to other proteins listed in the public database, and therefore, structural characterization of these proteins has played an integral role in functional assignment. These structural studies have not only provided insights into structure-function relationships but have also identified links between viruses across all three domains of life.

    更新日期:2019-11-01
  • Vaccine Development as a Means to Control Dengue Virus Pathogenesis: Do We Know Enough?
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2014-11-03
    Theodore C Pierson,Michael S Diamond

    Dengue virus (DENV) is a mosquito-transmitted RNA virus responsible for 390 million infections each year and significant morbidity and mortality throughout tropical and subtropical regions of the world. Efforts to develop a DENV vaccine span 70 years and include the work of luminaries of the virus vaccine field. Although vaccines have been used to reduce the global health burden of other flaviviruses, the unique requirement for a single vaccine to protect against four different groups of dengue viruses, and the link between secondary infections and DENV disease pathogenesis, has limited success to date. In this review, we discuss several promising DENV vaccine candidates in clinical trials and assess how recent advances in understanding of DENV biology and immunity may expedite efforts toward the development of safe and effective vaccines.

    更新日期:2019-11-01
  • Human Cytomegalovirus: Coordinating Cellular Stress, Signaling, and Metabolic Pathways.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2014-11-03
    Thomas Shenk,James C Alwine

    Viruses face a multitude of challenges when they infect a host cell. Cells have evolved innate defenses to protect against pathogens, and an infecting virus may induce a stress response that antagonizes viral replication. Further, the metabolic, oxidative, and cell cycle state may not be conducive to the viral infection. But viruses are fabulous manipulators, inducing host cells to use their own characteristic mechanisms and pathways to provide what the virus needs. This article centers on the manipulation of host cell metabolism by human cytomegalovirus (HCMV). We review the features of the metabolic program instituted by the virus, discuss the mechanisms underlying these dramatic metabolic changes, and consider how the altered program creates a synthetic milieu that favors efficient HCMV replication and spread.

    更新日期:2019-11-01
  • Polydnaviruses: Nature's Genetic Engineers.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2014-11-03
    Michael R Strand,Gaelen R Burke

    Virus-host associations are usually viewed as parasitic, but several studies in recent years have reported examples of viruses that benefit host organisms. The Polydnaviridae are of particular interest because these viruses are all obligate mutualists of insects called parasitoid wasps. Parasitoids develop during their immature stages by feeding inside the body of other insects, which serve as their hosts. Polydnaviruses are vertically transmitted as proviruses through the germ line of wasps but also function as gene delivery vectors that wasps rely upon to genetically manipulate the hosts they parasitize. Here we review the evolutionary origin of polydnaviruses, the organization and function of their genomes, and some of their roles in parasitism.

    更新日期:2019-11-01
  • Remarkable Mechanisms in Microbes to Resist Phage Infections.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2014-11-03
    Ron L Dy,Corinna Richter,George P C Salmond,Peter C Fineran

    Bacteriophages (phages) specifically infect bacteria and are the most abundant biological entities on Earth. The constant exposure to phage infection imposes a strong selective pressure on bacteria to develop viral resistance strategies that promote prokaryotic survival. Thus, this parasite-host relationship results in an evolutionary arms race of adaptation and counteradaptation between the interacting partners. The evolutionary outcome is a spectrum of remarkable strategies used by the bacteria and phages as they attempt to coexist. These approaches include adsorption inhibition, injection blocking, abortive infection, toxin-antitoxin, and CRISPR-Cas systems. In this review, we highlight the diverse and complementary antiphage systems in bacteria, as well as the evasion mechanisms used by phages to escape these resistance strategies.

    更新日期:2019-11-01
  • Cytoplasmic RNA Granules and Viral Infection.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2014-11-03
    Wei-Chih Tsai,Richard E Lloyd

    RNA granules are dynamic cellular structures essential for proper gene expression and homeostasis. The two principal types of cytoplasmic RNA granules are stress granules, which contain stalled translation initiation complexes, and processing bodies (P bodies), which concentrate factors involved in mRNA degradation. RNA granules are associated with gene silencing of transcripts; thus, viruses repress RNA granule functions to favor replication. This article discusses the breadth of viral interactions with cytoplasmic RNA granules, focusing on mechanisms that modulate the functions of RNA granules and that typically promote viral replication. Currently, mechanisms for virus manipulation of RNA granules can be loosely grouped into three nonexclusive categories: (a) cleavage of key RNA granule factors, (b) regulation of PKR activation, and (c) co-opting of RNA granule factors for new roles in viral replication. Viral modulation of RNA granules supports productive infection by inhibiting their gene-silencing functions and counteracting their role in linking stress sensing with innate immune activation.

    更新日期:2019-11-01
  • Glycan Engagement by Viruses: Receptor Switches and Specificity.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2014-11-03
    Luisa J Ströh,Thilo Stehle

    A large number of viruses, including many human pathogens, bind cell-surface glycans during the initial steps of infection. Viral glycan receptors such as glycosaminoglycans and sialic acid-containing carbohydrates are often negatively charged, but neutral glycans such as histo-blood group antigens can also function as receptors. The engagement of glycans facilitates attachment and entry and, consequently, is often a key determinant of the host range, tissue tropism, pathogenicity, and transmissibility of viruses. Here, we review current knowledge about virus-glycan interactions using representative crystal structures of viral attachment proteins in complex with glycans. We illuminate the determinants of specificity utilized by different glycan-binding viruses and explore the potential of these interactions for switching receptor specificities within or even between glycan classes. A detailed understanding of these parameters is important for the prediction of binding sites where structural information is not available, and is invaluable for the development of antiviral therapeutics.

    更新日期:2019-11-01
  • Viral Manipulation of Plant Host Membranes.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2014-11-03
    Jean-François Laliberté,Huanquan Zheng

    Plant viruses, like animal viruses, induce the formation of novel intracellular membranous structures that provide an optimum environment for coordinating diverse viral processes such as viral RNA synthesis and virus egress. Membrane reshaping is accomplished by the expression of specific membrane-associated viral proteins that interact with host proteins involved in membrane trafficking processes. Plant virus-induced membranous structures are motile, and this intracellular motility is required for the transport of viral RNA from sites of synthesis to plasmodesmata, which are used to move viral RNA from cell to cell. Cellular movement of these virus-induced bodies requires myosin motor activity and is dependent on the secretory pathway. The coupling of membrane-associated replication complexes with virus intra- and intercellular trafficking may explain why viral infection of neighboring cells is established rapidly and efficiently.

    更新日期:2019-11-01
  • Herpesvirus Genome Integration into Telomeric Repeats of Host Cell Chromosomes.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2014-11-03
    Nikolaus Osterrieder,Nina Wallaschek,Benedikt B Kaufer

    It is well known that numerous viruses integrate their genetic material into host cell chromosomes. Human herpesvirus 6 (HHV-6) and oncogenic Marek's disease virus (MDV) have been shown to integrate their genomes into host telomeres of latently infected cells. This is unusual for herpesviruses as most maintain their genomes as circular episomes during the quiescent stage of infection. The genomic DNA of HHV-6, MDV, and several other herpesviruses harbors telomeric repeats (TMRs) that are identical to host telomere sequences (TTAGGG). At least in the case of MDV, viral TMRs facilitate integration into host telomeres. Integration of HHV-6 occurs not only in lymphocytes but also in the germline of some individuals, allowing vertical virus transmission. Although the molecular mechanism of telomere integration is poorly understood, the presence of TMRs in a number of herpesviruses suggests it is their default program for genome maintenance during latency and also allows efficient reactivation.

    更新日期:2019-11-01
  • Mechanisms of Virus Membrane Fusion Proteins.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2014-11-03
    Margaret Kielian

    Enveloped viruses infect host cells by a membrane fusion reaction that takes place at the cell surface or in intracellular compartments following virus uptake. Fusion is mediated by the membrane interactions and conformational changes of specialized virus envelope proteins termed membrane fusion proteins. This article discusses the structures and refolding reactions of specific fusion proteins and the methods for their study and highlights outstanding questions in the field.

    更新日期:2019-11-01
  • The Placenta as a Barrier to Viral Infections.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2014-11-03
    Elizabeth Delorme-Axford,Yoel Sadovsky,Carolyn B Coyne

    Throughout pregnancy, the placenta acts as a physical and immunological barrier against the hematogenous transmission of viruses from mother to fetus. Despite this, very little is known regarding the specific mechanisms by which the placenta shields the developing fetus from viral infections or about the strategies utilized by select viruses to bypass and/or weaken the placental barrier. In this review, we summarize studies regarding virus-host interactions at the placental interface and explore key areas for future investigation. We focus our review on placental trophoblasts, which form the barrier between maternal and fetal circulations and thus govern the cross talk between the maternal and fetal microenvironments.

    更新日期:2019-11-01
  • Thinking Outside the Triangle: Replication Fidelity of the Largest RNA Viruses.
    Annu. Rev. Virol. (IF 6.566) Pub Date : 2014-11-03
    Everett Clinton Smith,Nicole R Sexton,Mark R Denison

    When judged by ubiquity, adaptation, and emergence of new diseases, RNA viruses are arguably the most successful biological organisms. This success has been attributed to a defect of sorts: high mutation rates (low fidelity) resulting in mutant swarms that allow rapid selection for fitness in new environments. Studies of viruses with small RNA genomes have identified fidelity determinants in viral RNA-dependent RNA polymerases and have shown that RNA viruses likely replicate within a limited fidelity range to maintain fitness. In this review we compare the fidelity of small RNA viruses with that of the largest RNA viruses, the coronaviruses. Coronaviruses encode the first known viral RNA proofreading exoribonuclease, a function that likely allowed expansion of the coronavirus genome and that dramatically increases replication fidelity and the range of tolerated variation. We propose models for regulation of coronavirus fidelity and discuss the implications of altered fidelity for RNA virus replication, pathogenesis, and evolution.

    更新日期:2019-11-01
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