Advances in Virus Research最新文献

Bluetongue virus (BTV) is an insect-vectored emerging pathogen of wild ruminants and livestock in many parts of the world. The virion particle is a complex structure of consecutive layers of protein surrounding a genome of 10 double-stranded (ds) RNA segments. BTV has been studied extensively as a model system for large, nonenveloped dsRNA viruses. A combination of recombinant proteins and particles together with reverse genetics, high-resolution structural analysis by X-ray crystallography and cryo-electron microscopy techniques have been utilized to provide an order for the assembly of the capsid shell and the protein sequestration required for it. Further, a reconstituted in vitro assembly system and RNA-RNA interaction assay, have defined the individual steps required for the assembly and packaging of the 10-segmented RNA genome. In addition, various microscopic techniques have been utilized to illuminate the stages of virus maturation and its egress via multiple pathways. These findings have not only given an overall understanding of BTV assembly and morphogenesis but also indicated that similar assembly and egress pathways are likely to be used by related viruses and provided an informed starting point for intervention or prevention.

The geminivirus capsid architecture is unique and built from twinned pseudo T=1 icosahedrons with 110 copies of the coat protein (CP). The CP is multifunctional. It performs various functions during the infection of a wide range of agriculturally important plant hosts. The CP multimerizes via pentameric intermediates during assembly and encapsulates the ssDNA genome to generate the unique capsid morphology. The virus capsid protects and transports the genome in the insect vector and plant host enroute to the plant nucleus for replication and the production of progeny. This review further explores CP:CP and CP:DNA interactions, and the environmental conditions that govern the assembly of the geminivirus capsid. This analysis was facilitated by new data available for the family, including three-dimensional structures and molecular biology data for several members. In addition, current and promising new control strategies of plant crop infection, which can lead to starvation for subsistence farmers, are discussed.

It has been over 100 years since the 1918 influenza pandemic, one of the most infamous examples of viral immunopathology. Since that time, there has been an inevitable repetition of influenza pandemics every few decades and yearly influenza seasons, which have a significant impact on human health. Recently, noteworthy progress has been made in defining the cellular and molecular mechanisms underlying pathology induced by an exuberant host response to influenza virus infection. Infection with influenza viruses is associated with a wide spectrum of disease, from mild symptoms to severe complications including respiratory failure, and the severity of influenza disease is driven by a complex interplay of viral and host factors. This chapter will discuss mechanisms of infection severity using concepts of disease resistance and tolerance as a framework for understanding the balance between viral clearance and immunopathology. We review mechanistic studies in animal models of infection and correlational studies in humans that have begun to define these factors and discuss promising host therapeutic targets to improve outcomes from severe influenza disease.

Nucleocytoviricota viruses (NCVs) belong to a newly established phylum originally grouped as Nucleocytoplasmic large DNA viruses. NCVs are unique because of their large and complicated genomes that contain cellular genes with homologs from all kingdoms of life, raising intensive debates on their evolutional origins. Many NCVs pack their genomes inside massive icosahedral capsids assembled from thousands of proteins. Studying the assembly mechanism of such capsids has been challenging until breakthroughs from structural studies. Subsequently, several models of the capsid assembly were proposed, which provided some interesting insights on this elaborate process. In this review, we discuss three of the most recent assembly models as well as supporting experimental observations. Furthermore, we propose a new model that combines research developments from multiple sources. Investigation of the assembly process of these vast NCV capsids will facilitate future deciphering of the molecular mechanisms driving the formation of similar supramolecular complexes.

The flavivirus genus encompasses more than 75 unique viruses, including dengue virus which accounts for almost 390 million global infections annually. Flavivirus infection can result in a myriad of symptoms ranging from mild rash and flu-like symptoms, to severe encephalitis and even hemorrhagic fever. Efforts to combat the impact of these viruses have been hindered due to limited antiviral drug and vaccine development. However, the advancement of knowledge in the structural biology of flaviviruses over the last 25 years has produced unique perspectives for the identification of potential therapeutic targets. With particular emphasis on the assembly and maturation stages of the flavivirus life cycle, it is the goal of this review to comparatively analyze the structural similarities between flaviviruses to provide avenues for new research and innovation.

Mixed viral infections occur more commonly than would be expected by chance in nature. Virus-virus interactions may affect viral traits and leave a genetic signature in the population, and thus influence the prevalence and emergence of viral diseases. Understanding about how the interactions between viruses within a host shape the evolutionary dynamics of the viral populations is needed for viral disease prevention and management. Here, we first synthesize concepts implied in the occurrence of virus-virus interactions. Second, we consider the role of the within-host interactions of virus-virus and virus-other pathogenic microbes, on the composition and structure of viral populations. Third, we contemplate whether mixed viral infections can create opportunities for the generation and maintenance of viral genetic diversity. Fourth, we attempt to summarize the evolutionary response of viral populations to mixed infections to understand how they shape the spatio-temporal dynamics of viral populations at the individual plant and field scales. Finally, we anticipate the future research under the reconciliation of molecular epidemiology and evolutionary ecology, drawing attention to the need of adding more complexity to future research in order to gain a better understanding about the mechanisms operating in nature.

Organisms clear infections by mounting an immune response that is normally turned off once the pathogens have been cleared. However, sometimes this immune response is not properly or timely arrested, resulting in the host damaging itself. This immune dysregulation may be referred to as immunopathology. While our knowledge of immune and metabolic pathways in insects, particularly in response to viral infections, is growing, little is known about the mechanisms that regulate this immune response and hence little is known about immunopathology in this important and diverse group of organisms. In this chapter we focus both on documenting the molecular mechanisms described involved in restoring immune homeostasis in insects after viral infections and on identifying potential mechanisms for future investigation. We argue that learning about the immunopathological consequences of an improperly regulated immune response in insects will benefit both insect and human health.