Annual Review of Virology最新文献

Bacteriophages and bacterial biofilms are widely present in natural environments, a fact that has accelerated the evolution of phages and their bacterial hosts in these particular niches. Phage-host interactions in biofilm communities are rather complex, where phages are not always merely predators but also can establish symbiotic relationships that induce and strengthen biofilms. In this review we provide an overview of the main features affecting phage-biofilm interactions as well as the currently available methods of studying these interactions. In addition, we address the applications of phages for biofilm control in different contexts.

The saying "It takes a village to raise a child" has never been truer than in my case. This autobiographical article documents my growing up and working on three different continents and my influencers along the way. Born in a village in Nigeria, West Africa, I spent the first 12 years of life with my grandmother living in a mud house and attending a village primary school. I walked barefoot to school every day, learned to read, and wrote on a chalk slate. At the age of 13, I moved to my second "village," London, England. In secondary school my love of science began to blossom. I attained a double major in chemistry and human biology from the University of Hertfordshire and a PhD in biophysics from the University of London, with a research project aimed at designing anticancer agents. I was mentored by Terence Jenkins and Stephen Neidle. For my postdoctoral training, I crossed the ocean again, to the United States, my third "village." In Michael Rossmann's group at Purdue University, my love for viruses was ignited. My independent career in structural virology began at Warwick University, England, working on pathogenic single-stranded DNA packaging viruses. In 2020, I am a full professor at the University of Florida. Most of my research is focused on the adeno-associated viruses, gene delivery vectors. My list of mentors has grown and includes Nick Muzyczka. Here, the mentee has become the mentor, and along the way, we attained a number of firsts in the field of structural virology and contributed to the field at the national and international stages.

Chronic hepatitis B virus (HBV) infection is the leading cause of liver cirrhosis and hepatocellular carcinoma, estimated to be globally responsible for ∼800,000 deaths annually. Although effective vaccines are available to prevent new HBV infection, treatment of existing chronic hepatitis B (CHB) is limited, as the current standard-of-care antiviral drugs can only suppress viral replication without achieving cure. In 2016, the World Health Organization called for the elimination of viral hepatitis as a global public health threat by 2030. The United States and other nations are working to meet this ambitious goal by developing strategies to cure CHB, as well as prevent HBV transmission. This review considers recent research progress in understanding HBV pathobiology and development of therapeutics for the cure of CHB, which is necessary for elimination of hepatitis B by 2030.

Viral quasispecies are dynamic distributions of nonidentical but closely related mutant and recombinant viral genomes subjected to a continuous process of genetic variation, competition, and selection that may act as a unit of selection. The quasispecies concept owes its theoretical origins to a model for the origin of life as a collection of mutant RNA replicators. Independently, experimental evidence for the quasispecies concept was obtained from sampling of bacteriophage clones, which revealed that the viral populations consisted of many mutant genomes whose frequency varied with time of replication. Similar findings were made in animal and plant RNA viruses. Quasispecies became a theoretical framework to understand viral population dynamics and adaptability. The evidence came at a time when mutations were considered rare events in genetics, a perception that was to change dramatically in subsequent decades. Indeed, viral quasispecies was the conceptual forefront of a remarkable degree of biological diversity, now evident for cell populations and organisms, not only for viruses. Quasispecies dynamics unveiled complexities in the behavior of viral populations,with consequences for disease mechanisms and control strategies. This review addresses the origin of the quasispecies concept, its major implications on both viral evolution and antiviral strategies, and current and future prospects.

Combinatory antiretroviral therapy (cART) reduces human immunodeficiency virus type 1 (HIV-1) replication but is not curative because cART interruption almost invariably leads to a rapid rebound of viremia due to the persistence of stable HIV-1-infected cellular reservoirs. These reservoirs are mainly composed of CD4⁺ T cells harboring replication-competent latent proviruses. A broadly explored approach to reduce the HIV-1 reservoir size, the shock and kill strategy, consists of reactivating HIV-1 gene expression from the latently infected cellular reservoirs (the shock), followed by killing of the virus-producing infected cells (the kill). Based on improved understanding of the multiple molecular mechanisms controlling HIV-1 latency, distinct classes of latency reversing agents (LRAs) have been studied for their efficiency to reactivate viral gene expression in in vitro and ex vivo cell models. Here, we provide an up-to-date review of these different mechanistic classes of LRAs and discuss optimizations of the shock strategy by combining several LRAs simultaneously or sequentially.

Over the past decades, there have been tremendous efforts to understand the cross-talk between viruses and host metabolism. Several studies have elucidated the mechanisms through which viral infections manipulate metabolic pathways including glucose, fatty acid, protein, and nucleotide metabolism. These pathways are evolutionarily conserved across the tree of life and extremely important for the host's nutrient utilization and energy production. In this review, we focus on host glucose, glutamine, and fatty acid metabolism and highlight the pathways manipulated by the different classes of viruses to increase their replication. We also explore a new system of viral hormones in which viruses mimic host hormones to manipulate the host endocrine system. We discuss viral insulin/IGF-1-like peptides and their potential effects on host metabolism. Together, these pathogenesis mechanisms targeting cellular signaling pathways create a multidimensional network of interactions between host and viral proteins. Defining and better understanding these mechanisms will help us to develop new therapeutic tools to prevent and treat viral infections.

Techniques for atomic-resolution structural biology have evolved during the past several decades. Breakthroughs in instrumentation, sample preparation, and data analysis that occurred in the past decade have enabled characterization of viruses with an unprecedented level of detail. Here we review the recent advances in magic-angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy for structural analysis of viruses and viral assemblies. MAS NMR is a powerful method that yields information on 3D structures and dynamics in a broad range of experimental conditions. After a brief introduction, we discuss recent structural and functional studies of several viruses investigated with atomic resolution at various levels of structural organization, from individual domains of a membrane protein reconstituted into lipid bilayers to virus-like particles and intact viruses. We present examples of the unique information revealed by MAS NMR about drug binding, conduction mechanisms, interactions with cellular host factors, and DNA packaging in biologically relevant environments that are inaccessible by other methods.

Viral fusion glycoproteins catalyze membrane fusion during viral entry. Unlike most enzymes, however, they lack a conventional active site in which formation or scission of a specific covalent bond is catalyzed. Instead, they drive the membrane fusion reaction by cojoining highly regulated changes in conformation to membrane deformation. Despite the challenges in applying inhibitor design approaches to these proteins, recent advances in knowledge of the structures and mechanisms of viral fusogens have enabled the development of small-molecule inhibitors of both class I and class II viral fusion proteins. Here, we review well-validated inhibitors, including their discovery, targets, and mechanism(s) of action, while highlighting mechanistic similarities and differences. Together, these examples make a compelling case for small-molecule inhibitors as tools for probing the mechanisms of viral glycoprotein-mediated fusion and for viral glycoproteins as druggable targets.

Viroids are small, single-stranded, circular RNAs infecting plants. Composed of only a few hundred nucleotides and being unable to code for proteins, viroids represent the lowest level of complexity for an infectious agent, even below that of the smallest known viruses. Despite the relatively small size, viroids contain RNA structural elements embracing all the information needed to interact with host factors involved in their infectious cycle, thus providing models for studying structure-function relationships of RNA. Viroids are specifically targeted to nuclei (family Pospiviroidae) or chloroplasts (family Avsunviroidae), where replication based on rolling-circle mechanisms takes place. They move locally and systemically through plasmodesmata and phloem, respectively, and may elicit symptoms in the infected host, with pathogenic pathways linked to RNA silencing and other plant defense responses. In this review, recent advances in the dissection of the complex interplay between viroids and plants are presented, highlighting knowledge gaps and perspectives for future research.

At the time I entered college and for a few years afterward, I had very few concrete goals. Hence, my progress was more a matter of luck than planning and was somewhat analogous to a small wood chip floating down a slow stream, bumping into various objects tossed and turned hither and thither, all the while being surrounded by larger and more appealing chips. I have been extremely lucky to have been associated with numerous helpful and knowledgeable mentors, colleagues, postdocs, students, and coworkers whose advice had major impacts on my life. Therefore, throughout this article, I have attempted to acknowledge central individuals who contributed to my progress in academia and to highlight the positive bumps to my chip on the steam that affected the directions of my career.