Advances in Virus Research最新文献

Knowledge of mycovirus diversity, evolution, horizontal gene transfer and shared ancestry with viruses infecting distantly related hosts, such as plants and arthropods, has increased vastly during the last few years due to advances in the high throughput sequencing methodologies. This also has enabled the discovery of novel mycoviruses with previously unknown genome types, mainly new positive and negative single-stranded RNA mycoviruses ((+) ssRNA and (-) ssRNA) and single-stranded DNA mycoviruses (ssDNA), and has increased our knowledge of double-stranded RNA mycoviruses (dsRNA), which in the past were thought to be the most common viruses infecting fungi. Fungi and oomycetes (Stramenopila) share similar lifestyles and also have similar viromes. Hypothesis about the origin and cross-kingdom transmission events of viruses have been raised and are supported by phylogenetic analysis and by the discovery of natural exchange of viruses between different hosts during virus-fungus coinfection in planta. In this review we make a compilation of the current information on the genome organization, diversity and taxonomy of mycoviruses, discussing their possible origins. Our focus is in recent findings suggesting the expansion of the host range of many viral taxa previously considered to be exclusively fungal, but we also address factors affecting virus transmissibility and coexistence in single fungal or oomycete isolates, as well as the development of synthetic mycoviruses and their use in investigating mycovirus replication cycles and pathogenicity.

Imaging pathogens within 3D environment of biological tissues provides spatial information about their localization and interactions with the host. Technological advances in fluorescence microscopy and 3D image analysis now permit visualization and quantification of pathogens directly in large tissue volumes and in great detail. In recent years large volume imaging became an important tool in virology research helping to understand the properties of viruses and the host response to infection. In this chapter we give a review of fluorescence microscopy modalities and tissue optical clearing methods used for large volume tissue imaging. A summary of recent applications for virus research is provided with particular emphasis on studies using light sheet fluorescence microscopy. We describe the challenges and approaches for volumetric image analysis. Practical examples of volumetric imaging implemented in virology laboratories and addressing specialized research questions, such as virus tropism and immune host response are described. We conclude with an overview of the emerging technologies and their potential for virus research.

Rift Valley Fever Virus (RVFV) is a negative sense segmented RNA virus that can cause severe hemorrhagic fever. The tri-segmented virus genome encodes for six (6) multifunctional proteins that engage host factors at a variety of different stages in the replication cycle. The S segment encodes nucleoprotein (N) and nonstructural protein S (NSs), the M segment encodes viral glycoproteins Gn and Gc as well as nonstructural protein M (NSm) and the L segment encodes the viral polymerase (L). Viral glycoproteins Gn and Gc are responsible for entry by binding to a number of host factors. Our recent studies identified a scavenger receptor, LDL receptor related protein 1 (Lrp1), as a potential pro-viral host factor for RVFV and related viruses, including Oropouche virus (OROV) infection. Coincidentally, several recent studies identified other LDL family proteins as viral entry factors and receptors for other viral families. Collectively, these observations suggest that highly conserved LDL family proteins may play a significant role in facilitating entry of viruses from several distinct families. Given the significant roles of viral and host factors during infection, characterization of these interactions is critical for therapeutic targeting with neutralizing antibodies and vaccines.

While many viral infections are limited and eventually resolved by the host immune response or by death of the host, other viruses establish long-term relationships with the host by way of a persistent infection, that range from chronic viruses that may be eventually cleared to those that establish life-long persistent or latent infection. Viruses infecting hosts from bacteria to humans establish quiescent infections that must be reactivated to produce progeny. For mammalian viruses, most notably herpesviruses, this quiescent maintenance of viral genomes in the absence of virus replication is referred to as latency. The latent strategy allows the virus to persist quiescently within a single host until conditions indicate a need to reactivate to reach a new host or, to re-seed a reservoir within the host. Here, I review common themes in viral strategies to regulate the latent cycle and reactivate from it ranging from bacteriophage to herpesviruses with a focus on human cytomegalovirus (HCMV). Themes central to herpesvirus latency include, epigenetic repression of viral gene expression and mechanisms to regulate host signaling and survival. Critical to the success of a latent program are mechanisms by which the virus can "sense" fluctuations in host biology (within the host) or environment (outside the host) and make appropriate "decisions" to maintain latency or re-initiate the replicative program. The signals or environments that indicate the establishment of a latent state, the very nature of the latent state, as well as the signals driving reactivation have been topics of intense study from bacteriophage to human viruses, as these questions encompass the height of complexity in virus-host interactions-where the host and the virus coexist.

Enteroviruses are among the most common viral infectious agents of humans and cause a broad spectrum of illness, which can range from mild and self-limiting to severe. Severe outcomes of enteroviral infections can include aseptic meningitis, bronchitis, acute liver failure, hand-foot-mouth disease (HFMD), hemorrhagic conjunctivitis, or acute flaccid myelitis and other paralytic syndromes. Enteroviruses initiate their replicative life cycles by attaching to a broad range of cell surface receptors, which play direct roles in the clinical outcomes of enteroviral infections. In this chapter, we review the transmission and viral life cycle of enteroviruses and discuss the diverse cell surface receptors that facilitate enterovirus attachment, entry, or genome release.

Rabies infects all mammals; however, transmission cycles are only maintained in certain bat and carnivore species. The high incidence of rabies in Greater Kudu (Tragelaphus strepsiceros) observed in Namibia for over 40 years has led to postulation that independent virus transmission is occurring within this antelope population. We have analysed extensive experimental, epidemiological, phylogeographic and deep sequence data, which collectively refute maintenance of an independent rabies cycle in kudu. As rabies in kudu continues to have a negative impact on the Namibian agricultural sector, measures to protect kudu have been investigated, including the use of a third-generation oral rabies vaccine. Initial results show protection of kudu from rabies infection via the oral route, with an appropriate bait design, different application schedules and vaccination doses further enhancing the immune response. Rabies in kudu is a complex interplay at the wildlife-livestock interface and requires a concerted approach to successfully control.

Reverse genetics is the prospective analysis of how genotype determines phenotype. In a typical experiment, a researcher alters a viral genome, then observes the phenotypic outcome. Among RNA viruses, this approach was first applied to positive-strand RNA viruses in the mid-1970s and over nearly 50 years has become a powerful and widely used approach for dissecting the mechanisms of viral replication and pathogenesis. During this time the global health importance of two virus groups, flaviviruses (genus Flavivirus, family Flaviviridae) and betacoronaviruses (genus Betacoronavirus, subfamily Orthocoronavirinae, family Coronaviridae), have dramatically increased, yet these viruses have genomes that are technically challenging to manipulate. As a result, several new techniques have been developed to overcome these challenges. Here I briefly review key historical aspects of positive-strand RNA virus reverse genetics, describe some recent reverse genetic innovations, particularly as applied to flaviviruses and coronaviruses, and discuss their benefits and limitations within the larger context of rigorous genetic analysis.

Methylation at the N⁶-position of either adenosine (m⁶A) or 2'-O-methyladenosine (m⁶Am) represents two of the most abundant internal modifications of coding and non-coding RNAs, influencing their maturation, stability and function. Additionally, although less abundant and less well-studied, monomethylation at the N¹-position (m¹A) can have profound effects on RNA folding. It has been known for several decades that RNAs produced by both DNA and RNA viruses can be m⁶A/m⁶Am modified and the list continues to broaden through advances in detection technologies and identification of the relevant methyltransferases. Recent studies have uncovered varied mechanisms used by viruses to manipulate the m⁶A pathway in particular, either to enhance virus replication or to antagonize host antiviral defenses. As such, RNA modifications represent an important frontier of exploration in the broader realm of virus-host interactions, and this new knowledge already suggests exciting opportunities for therapeutic intervention. In this review we summarize the principal mechanisms by which m⁶A/m⁶Am can promote or hinder viral replication, describe how the pathway is actively manipulated by biomedically important viruses, and highlight some remaining gaps in understanding how adenosine methylation of RNA controls viral replication and pathogenesis.

Interactions between marine viruses and microbes are a critical part of the oceanic carbon cycle. The impacts of virus-host interactions range from short-term disruptions in the mobility of microbial biomass carbon to higher trophic levels through cell lysis (i.e., the viral shunt) to long-term reallocation of microbial biomass carbon to the deep sea through accelerating the biological pump (i.e., the viral shuttle). The biogeochemical backdrop of the ocean-the physical, chemical, and biological landscape-influences the likelihood of both virus-host interactions and particle formation, and the fate and flow of carbon. As climate change reshapes the oceanic landscape through large-scale shifts in temperature, circulation, stratification, and acidification, virus-mediated carbon flux is likely to shift in response. Dynamics in the directionality and magnitude of changes in how, where, and when viruses mediate the recycling or storage of microbial biomass carbon is largely unknown. Integrating viral infection dynamics data obtained from experimental models and field systems, with particle motion microphysics and global observations of oceanic biogeochemistry, into improved ecosystem models will enable viral oceanographers to better predict the role of viruses in marine carbon cycling in the future ocean.

Alphaviruses are a large group (>30 species) of enveloped, positive-strand RNA viruses. The re-emergence of mosquito-transmitted alphaviruses associated with human diseases ranging from severe and potentially fatal neurological disease to chronic arthritic disease highlights the need to understand the biology and pathogenesis of alphaviruses. Here, we review the development and use of animal models of alphavirus transmission and human disease, and discuss areas for continued refinement of these models including possible avenues for future investigation.