Advances in Virus Research最新文献

Alphaviruses, members of the enveloped, positive-sense, single-stranded RNA Togaviridae family, represent a reemerging public health threat as mosquito vectors expand into new geographic territories. The Old World alphaviruses, which include chikungunya virus, Ross River virus, and Sindbis virus, tend to cause a clinical syndrome characterized by fever, rash, and arthritis, whereas the New World alphaviruses, which consist of Venezuelan equine encephalitis virus, eastern equine encephalitis virus, and western equine encephalitis virus, induce encephalomyelitis. Following recovery from the acute phase of infection, many patients are left with debilitating persistent joint and neurological complications that can last for years. Clues from human cases and studies using animal models strongly suggest that much of the disease and pathology induced by alphavirus infection, particularly atypical and chronic manifestations, is mediated by the immune system rather than directly by the virus. This review discusses the current understanding of the immunopathogenesis of the arthritogenic and neurotropic alphaviruses accumulated through both natural infection of humans and experimental infection of animals, particularly mice. As treatment following alphavirus infection is currently limited to supportive care, understanding the contribution of the immune system to the disease process is critical to developing safe and effective therapies.

Positive-strand RNA viruses need to arrogate many cellular resources to support their replication and infection cycles. These viruses co-opt host factors, lipids and subcellular membranes and exploit cellular metabolites to built viral replication organelles in infected cells. However, the host cells have their defensive arsenal of factors to protect themselves from easy exploitation by viruses. In this review, the author discusses an emerging arms race for cellular resources between viruses and hosts, which occur during the early events of virus-host interactions. Recent findings with tomato bushy stunt virus and its hosts revealed that the need of the virus to exploit and co-opt given members of protein families provides an opportunity for the host to deploy additional members of the same or associated protein family to interfere with virus replication. Three examples with well-established heat shock protein 70 and RNA helicase protein families and the ubiquitin network will be described to illustrate this model on the early arms race for cellular resources between tombusviruses and their hosts. We predict that arms race for resources with additional cellular protein families will be discovered with tombusviruses. These advances will fortify research on interactions among other plant and animal viruses and their hosts.

Phenotypic plasticity enables organisms to survive in the face of unpredictable environmental stress. Intimately related to the notion of phenotypic plasticity is the concept of the reaction norm that places phenotypic plasticity in the context of a genotype-specific response to environmental gradients. Whether reaction norms themselves evolve and which factors might affect their shape has been the object of intense debates among evolutionary biologists along the years. Since their discovery, viruses have been considered as pathogens. However, new viromic techniques and a shift in conceptual paradigms are showing that viruses are mostly non-pathogenic ubiquitous entities. Recent studies have shown how viral infections can even be beneficial for their hosts. This may happen especially in the context of stressed hosts, where the virus infection can induce beneficial changes in the host's physiological homeostasis, hence changing the shape of the reaction norm. Despite the fact that underlying physiological mechanisms and evolutionary dynamics are still not well understood, such beneficial interactions are being discovered in a growing number of plant-virus systems. Here, we aim to review these disperse studies and place them into the context of phenotypic plasticity and the evolution of reaction norms. This is an emerging field that is posing many questions that still need to be properly answered. The answers would clearly interest virologists, plant pathologists and evolutionary biologists and likely they will suggest possible future biotechnological applications, including the development of crops with higher survival rates and yield under adverse environmental situations.

Potyvirus genus clusters a significant and expanding number of widely distributed plant viruses, responsible for large losses impacting most crops of economic interest. The potyviral genome is a single-stranded, linear, positive-sense RNA of around 10kb that is encapsidated in flexuous rod-shaped filaments, mostly made up of a helically arranged coat protein (CP). Beyond its structural role of protecting the viral genome, the potyviral CP is a multitasking protein intervening in practically all steps of the virus life cycle. In particular, interactions between the CP and the viral RNA must be tightly controlled to allow the correct assignment of the RNA to each of its functions through the infection process. This review attempts to bring together the most relevant available information regarding the architecture and modus operandi of potyviral CP and virus particles, highlighting significant discoveries, but also substantial gaps in the existing knowledge on mechanisms orchestrating virion assembly and disassembly. Biotechnological applications based on potyvirus nanoparticles is another important topic addressed here.

Adeno-associated virus (AAV) is a nonenveloped, ssDNA virus in the parvovirus family, which has become one of the leading candidate vectors for human gene therapy. AAV has been studied extensively to identify host cellular factors involved in infection, as well as to identify capsid variants that confer clinically favorable transduction profiles ex vivo and in vivo. Recent advances in technology have allowed for direct genetic approaches to be used to more comprehensively characterize host factors required for AAV infection and allowed for identification of a critical multi-serotype receptor, adeno-associated virus receptor (AAVR). In this chapter, we will discuss the interactions of AAV with its glycan and proteinaceous receptors and describe the host and viral components involved in AAV entry, which requires cellular attachment, endocytosis, trafficking to the trans-Golgi network and nuclear import. AAV serves as a paradigm for entry of nonenveloped viruses. Furthermore, we will discuss the potential of utilizing our increased understanding of virus-host interactions during AAV entry to develop better AAV-based therapeutics, with a focus on host factors and capsid interactions involved in in vivo tropism.

Influenza A virus (IAV) is an enveloped virus of the Orthomyxoviridae with a negative-sense single-stranded RNA genome. During virus cell entry, viral and cellular cues are delivered in a stepwise manner within two distinct cellular compartments-the endosomes and the cytosol. Endosome maturation primes the viral core for uncoating by cytosolic host proteins and host-mediated virus disaggregation is essential for genome import and replication in the nucleus. Recent evidence shows that two well-known cellular proteins-histone deacetylase 6 (HDAC6) and karyopherin-β2 (kapβ2)-uncoat influenza virus. HDAC6 is 1 of 11 HDACs and an X-linked, cytosolic lysine deacetylase. Under normal cellular conditions HDAC6 is the tubulin deacetylase. Under proteasomal stress HDAC6 binds unanchored ubiquitin, dynein and myosin II to sequester misfolded protein aggregates for autophagy. Kapβ2 is a member of the importin β family that transports RNA-binding proteins into the nucleus by binding to disordered nuclear localization signals (NLSs) known as PY-NLS. Kapβ2 is emerging as a universal uncoating factor for IAV and human immunodeficiency virus type 1 (HIV-1). Kapβ2 can also reverse liquid-liquid phase separation (LLPS) of RNA-binding proteins by promoting their disaggregation. Thus, it is becoming evident that key players in the management of cellular condensates and membraneless organelles are potent virus uncoating factors. This emerging concept reveals implications in viral pathogenesis, as well as, the promise for cell-targeted therapeutic strategies to block universal virus uncoating pathways hijacked by enveloped RNA viruses.

The phenotypic manifestations of disease induced by viruses and subviral infectious entities are the result of complex molecular interactions between host and viral factors. The viral determinants of the diseased phenotype have traditionally been sought at the level of structural or non-structural proteins. However, the discovery of RNA silencing mechanisms has led to speculations that determinants of the diseased phenotype are caused by viral nucleic acid sequences in addition to proteins. RNA silencing is a gene regulation mechanism conserved within eukaryotic kingdoms (with the exception of some yeast species), and in plants and insects it also functions as an antiviral mechanism. Non-coding RNAs of viral origin, ranging in size from 21 to 24 nucleotides (viral small interfering RNAs, vsiRNAs) accumulate in virus-infected tissues and organs, in some cases to comparable levels as the entire complement of host-encoded small interfering RNAs. Upon incorporation into RNA-induced silencing complexes, vsiRNAs can mediate cleavage or induce translational inhibition of nucleic acid targets in a sequence-specific manner. This review focuses on recent findings that suggest an increased complexity of small RNA-based interactions between virus and host. We mainly address plant viruses, but where applicable discuss insect viruses as well. Prominence is given to studies that have indisputably demonstrated that vsiRNAs determine diseased phenotype by either carrying sequence determinants or, indirectly, by altering host-gene regulatory pathways. Results from these studies suggest biotechnological applications, which are also discussed.

Knowledge on bornaviruses has expanded tremendously during the last decade through detection of novel bornaviruses and endogenous bornavirus-like elements in many eukaryote genomes, as well as by confirmation of insectivores as reservoir species for classical Borna disease virus 1 (BoDV-1). The most intriguing finding was the demonstration of the zoonotic potential of lethal human bornavirus infections caused by a novel bornavirus of different squirrel species (variegated squirrel 1 bornavirus, VSBV-1) and by BoDV-1 known as the causative agent for the classical Borna disease in horses and sheep. Whereas a T cell-mediated immunopathology has already been confirmed as key disease mechanism for infection with BoDV-1 by experimental studies in rodents, the underlying pathomechanisms remain less clear for human bornavirus infections, infection with other bornaviruses or infection of reservoir species. Thus, an overview of current knowledge on the pathogenesis of bornavirus infections focusing on immunopathology is given.