Advances in Virus Research最新文献

Human maximum containment facilities-also known as biosafety level 4 (BSL-4) laboratories-for zoonotic viruses such as Ebola virus or Nipah virus and veterinary maximum containment (BSL-4vet) facilities, e.g. for foot-and-mouth disease virus or peste-de-petits-ruminants virus, share many similar features but also differ in their design, standard operating procedures and operational requirements. This article summarizes the similarities and differences by addressing relevant aspects of these two types of maximum containment facilities. Construction and operation of both facilities is bound by strict regulations and regular audits by national or state authorities. The technical infrastructure is similar with respect to air handling, negative pressure differential to the outside and between rooms, as well as autoclaves and waste water handling. Both facilities require strict access control and training for entry into the area, which is more extensive on the human maximum containment side. Special personal protective equipment such as a positive pressure suits needs to be worn in the human maximum containment facility, but this is not generally necessary in veterinary facilities. Exiting the facility requires showering of personnel-a personal shower only in the veterinary containment and at least a chemical shower to decontaminate the suit in the human containment. Removal of samples from both kinds of facilities can only occur after application of strict and validated inactivation protocols. In addition, both facilities undergo room decontamination processes for maintenance or between animal studies. Overall, we would like to demonstrate that these facilities have more in common than expected at first glance and close coordination and cooperation between the individuals responsible for them is advisable.

Sudan virus (SUDV) causes highly lethal outbreaks of hemorrhagic disease throughout Africa, but there has yet to be an approved vaccine or therapeutic to combat this public health threat. The most common route of natural exposure to filoviruses is through mucosal contact which greatly impacts initial viral replication. Historically, SUDV animal models used an intramuscular infection route. Here, we sought to further characterize an animal model using mucosal challenge routes and compared the impact that intramuscular, intranasal, or aerosol exposure had on SUDV pathogenicity in a ferret model. We determined that the route of infection did not significantly impact overall SUDV pathogenicity; only subtle changes were detected in magnitude of viremia and oral viral shedding. Additionally, we sought to determine if preexisting Lloviu virus (LLOV) immunity could protect ferrets from lethal SUDV infection. We found that the previous immunity elicited by LLOV infection was not sufficient to protect ferrets from lethal SUDV disease. In conclusion, our results indicate that the infection route has minimal effect on overall pathogenicity of SUDV in ferrets and that prior LLOV infection does not elicit a cross-protective immune response to SUDV.

Resistance to infection by plant viruses involves proteins encoded by plant resistance (R) genes, viz., nucleotide-binding leucine-rich repeats (NLRs), immune receptors. These sensor NLRs are activated either directly or indirectly by viral protein effectors, in effector-triggered immunity, leading to induction of defense signaling pathways, resulting in the synthesis of numerous downstream plant effector molecules that inhibit different stages of the infection cycle, as well as the induction of cell death responses mediated by helper NLRs. Early events in this process involve recognition of the activation of the R gene response by various chaperones and the transport of these complexes to the sites of subsequent events. These events include activation of several kinase cascade pathways, and the syntheses of two master transcriptional regulators, EDS1 and NPR1, as well as the phytohormones salicylic acid, jasmonic acid, and ethylene. The phytohormones, which transit from a primed, resting states to active states, regulate the remainder of the defense signaling pathways, both directly and by crosstalk with each other. This regulation results in the turnover of various suppressors of downstream events and the synthesis of various transcription factors that cooperate and/or compete to induce or suppress transcription of either other regulatory proteins, or plant effector molecules. This network of interactions results in the production of defense effectors acting alone or together with cell death in the infected region, with or without the further activation of non-specific, long-distance resistance. Here, we review the current state of knowledge regarding these processes and the components of the local responses, their interactions, regulation, and crosstalk.

The surfaces of cells and enveloped viruses alike are coated in carbohydrates that play multifarious roles in infection and immunity. Organisms across all kingdoms of life make use of a diverse set of monosaccharide subunits, glycosidic linkages, and branching patterns to encode information within glycans. Accordingly, sugar-patterning enzymes and glycan binding proteins play integral roles in cell and organismal biology, ranging from glycoprotein quality control within the endoplasmic reticulum to lymphocyte migration, coagulation, inflammation, and tissue homeostasis. Unsurprisingly, genes involved in generating and recognizing oligosaccharide patterns are playgrounds for evolutionary conflicts that abound in cross-species interactions, exemplified by the myriad plant lectins that function as toxins. In vertebrates, glycans bearing acidic nine-carbon sugars called sialic acids are key regulators of immune responses. Various bacterial and fungal pathogens adorn their cells in sialic acids that either mimic their hosts' or are stolen from them. Yet, how viruses commandeer host sugar-patterning enzymes to thwart immune responses remains poorly studied. Here, we review examples of viruses that interact with sialic acid-binding immunoglobulin-like lectins (Siglecs), a family of immune cell receptors that regulate toll-like receptor signaling and govern glycoimmune checkpoints, while highlighting knowledge gaps that merit investigation. Efforts to illuminate how viruses leverage glycan-dependent checkpoints may translate into new clinical treatments that uncloak viral antigens and infected cell surfaces by removing or masking immunosuppressive sialoglycans, or by inhibiting viral gene products that induce their biosynthesis. Such approaches may hold the potential to unleash the immune system to clear long intractable chronic viral infections.

Grapevine leafroll-associated virus 3 (GLRaV-3) is a major pathogen of grapevines worldwide resulting in grapevine leafroll disease (GLD), reduced fruit yield, berry quality and vineyard profitability. Being graft transmissible, GLRaV-3 is also transmitted between grapevines by multiple hemipteran insects (mealybugs and soft scale insects). Over the past 20 years, New Zealand has developed and utilized integrated pest management (IPM) solutions that have slowly transitioned to an ecosystem-based biological response to GLD. These IPM solutions and combinations are based on a wealth of research within the temperate climates of New Zealand's nation-wide grape production. To provide context, the grapevine viruses present in the national vineyard estate and how these have been identified are described; the most pathogenic and destructive of these is GLRaV-3. We provide an overview of research on GLRaV-3 genotypes and biology within grapevines and describe the progressive development of GLRaV-3/GLD diagnostics based on molecular, serological, visual, and sensor-based technologies. Research on the ecology and control of the mealybugs Pseudococcus calceolariae and P. longispinus, the main insect vectors of GLRaV-3 in New Zealand, is described together with the implications of mealybug biological control agents and prospects to enhance their abundance and/or fitness in the vineyard. Virus transmission by mealybugs is described, with emphasis on understanding the interactions between GLRaV-3, vectors, and plants (grapevines, alternative hosts, or non-hosts of the virus). Disease management through grapevine removal and the economic influence of different removal strategies is detailed. Overall, the review summarizes research by an interdisciplinary team working in close association with the national industry body, New Zealand Winegrowers. Teamwork and communication across the whole industry has enabled implementation of research for the management of GLD.

Schmallenberg virus, an arbovirus of the Orthobunyavirus genus that primarily infects ruminants, emerged in 2011 near the Dutch-German border region and subsequently caused a large number of abortions and the births of severely malformed newborns in the European livestock population. Immediate intensive research led to the development of reliable diagnostic tests, the identification of competent Culicoides vector species, and the elucidation of the pathogenesis in infected vertebrate hosts. In addition, the structure of the major antigenic domain has been elucidated in great detail, leading to the development of effective marker vaccine candidates. The knowledge gained over the last decade on the biology and pathogenesis of SBV and the experience acquired in its control will be of great value in the future for the control of any similar emerging pathogen of veterinary or public health importance such as Shuni or Oropouche virus. However, some important knowledge gaps remain, for example, the factors contributing to the highly variable transmission rate from dam to fetus or the viral factors responsible for the vector competence of Culicoides midges are largely unknown. Thus, questions still remain for the next decade of research on SBV and related viruses.

Norovirus infections are a leading cause of gastroenteritis worldwide. Despite the substantial global health burden and economic impact, there are currently no approved antiviral therapeutics or vaccines. Additionally, much of our knowledge of norovirus comes from experiments using surrogate viruses, such as murine norovirus and feline calicivirus. The challenge surrounding human norovirus research arises from a lack of robust cell culture systems and efficient animal models. In this review, we explore recent advances in the in vitro cultivation of human norovirus and reverse genetics systems and discuss commonly used in vivo models. We summarize the current understanding of both innate and adaptive immune responses to norovirus infection and provide an overview of vaccine strategies and the current clinical trial landscape, with a focus on the only vaccine candidate that has reached phase III clinical development stage.

RNA viruses are some of the most successful biological entities due their ability to adapt and evolve. Despite their small genome and parasitic nature, RNA viruses have evolved many mechanisms to ensure their survival and maintenance in the host population. We propose that one of these mechanisms of survival is the generation of nonstandard viral genomes (nsVGs) that accumulate during viral replication. NsVGs are often considered to be accidental defective byproducts of the RNA virus replication, but their ubiquity and the plethora of roles they have during infection indicate that they are an integral part of the virus life cycle. Here we review the different types of nsVGs and discuss how their multiple roles during infection could be beneficial for RNA viruses to be maintained in nature. By shifting our perspectives on what makes a virus successful, we posit that nsVG generation is a conserved phenomenon that arose during RNA virus evolution as an essential component of a healthy virus community.

G protein coupled receptors (GPCRs) are seven-transmembrane domain proteins that modulate cellular processes in response to external stimuli. These receptors represent the largest family of membrane proteins, and in mammals, their signaling regulates important physiological functions, such as vision, taste, and olfaction. Many organisms, including yeast, slime molds, and viruses encode GPCRs. Cytomegaloviruses (CMVs) are large, betaherpesviruses, that encode viral GPCRs (vGPCRs). Human CMV (HCMV) encodes four vGPCRs, including UL33, UL78, US27, and US28. Each of these vGPCRs, as well as their rodent and primate orthologues, have been investigated for their contributions to viral infection and disease. Herein, we discuss how the CMV vGPCRs function during lytic and latent infection, as well as our understanding of how they impact viral pathogenesis.

Usutu virus (USUV, Flaviviridae) is an emerging arbovirus that has led to epizootic outbreaks in birds and numerous human neuroinvasive disease cases in Europe. It is maintained in an enzootic cycle with Culex mosquitoes and passerine birds, a transmission cycle that is shared by West Nile virus (WNV) and St. Louis encephalitis virus (SLEV), two flaviviruses that are endemic in the United States. USUV and WNV co-circulate in Africa and Europe, and SLEV and WNV co-circulate in North America. These three viruses are prime examples of One Health issues, in which the interactions between humans, animals, and the environments they reside in can have important health impacts. The three facets of One Health are interwoven throughout this article as we discuss the mechanisms of flavivirus transmission and emergence. We explore the possibility of USUV emergence in the United States by analyzing the shared characteristics among USUV, WNV, and SLEV, including the role that flavivirus co-infections and sequential exposures may play in viral emergence. Finally, we provide insights on the importance of integrated surveillance programs as One Health tools that can be used to mitigate USUV emergence and spread.