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The Veterinary Clinics of North... Aug 2022A number of viruses transmitted by biological vectors or through direct contact, air, or ingestion cause neurologic disease in equids. Of interest are viruses of the... (Review)
Review
A number of viruses transmitted by biological vectors or through direct contact, air, or ingestion cause neurologic disease in equids. Of interest are viruses of the Togaviridae, Flaviviridae, Rhabdoviridae, Herpesviridae, Bornaviridae, and Bunyaviridae families. Many are classified as arboviruses because they use arthropod vectors, whereas others are transmitted directly via ingestion, inhalation, or integument damage. The goal of this article is to provide an overview on pathophysiologic and clinical aspects of arboviruses of equine importance, including alphaviruses (Togaviridae) and flaviviruses (Flaviviridae).
Topics: Alphavirus; Animals; Arboviruses; Flavivirus; Horse Diseases; Horses
PubMed: 35953146
DOI: 10.1016/j.cveq.2022.04.004 -
Advances in Virus Research 2020Alphaviruses, members of the enveloped, positive-sense, single-stranded RNA Togaviridae family, represent a reemerging public health threat as mosquito vectors expand...
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.
Topics: Alphavirus; Alphavirus Infections; Animals; Encephalitis Virus, Venezuelan Equine; Horses; Humans; Mice
PubMed: 32711733
DOI: 10.1016/bs.aivir.2020.06.002 -
Current Topics in Microbiology and... 2022Chikungunya virus (CHIKV) was discovered more than six decades ago, but has remained poorly investigated. However, after a recent outbreak of CHIK fever in both... (Review)
Review
Chikungunya virus (CHIKV) was discovered more than six decades ago, but has remained poorly investigated. However, after a recent outbreak of CHIK fever in both hemispheres and viral adaptation to new species of mosquitoes, it has attracted a lot of attention. The currently available experimental data suggest that molecular mechanisms of CHIKV replication in vertebrate and mosquito cells are similar to those of other New and Old World alphaviruses. However, this virus exhibits a number of unique characteristics that distinguish it from the other, better studied members of the alphavirus genus. This review is an attempt to summarize the data accumulated thus far regarding the molecular mechanisms of alphavirus RNA replication and interaction with host cells. Emphasis was placed on demonstrating the distinct features of CHIKV in utilizing host factors to build replication complexes and modify the intracellular environment for efficient viral replication and inhibition of the innate immune response. The available data suggest that our knowledge about alphavirus replication contains numerous gaps that potentially hamper the development of new therapeutic means against CHIKV and other pathogenic alphaviruses.
Topics: Animals; Chikungunya Fever; Chikungunya virus; Virus Replication; Viruses
PubMed: 30599050
DOI: 10.1007/82_2018_146 -
Viruses May 2015Alphavirus vectors present an attractive approach for gene therapy applications due to the rapid and simple recombinant virus particle production and their broad range... (Review)
Review
Alphavirus vectors present an attractive approach for gene therapy applications due to the rapid and simple recombinant virus particle production and their broad range of mammalian host cell transduction. Mainly three types of alphavirus vectors, namely naked RNA, recombinant particles and DNA/RNA layered vectors, have been subjected to preclinical studies with the goal of achieving prophylactic or therapeutic efficacy, particularly in oncology. In this context, immunization with alphavirus vectors has provided protection against challenges with tumor cells. Moreover, alphavirus intratumoral and systemic delivery has demonstrated substantial tumor regression and significant prolonged survival rates in various animal tumor models. Recent discoveries of the strong association of RNA interference and disease have accelerated gene therapy based approaches, where alphavirus-based gene delivery can play an important role.
Topics: Alphavirus; Cancer Vaccines; Drug Carriers; Genetic Therapy; Humans; Neoplasms; Transduction, Genetic
PubMed: 25961488
DOI: 10.3390/v7052321 -
Viruses Mar 2018Alphavirus nucleocapsids are assembled in the cytoplasm of infected cells from 240 copies of the capsid protein and the approximately 11 kb positive strand genomic RNA.... (Review)
Review
Alphavirus nucleocapsids are assembled in the cytoplasm of infected cells from 240 copies of the capsid protein and the approximately 11 kb positive strand genomic RNA. However, the challenge of how the capsid specifically selects its RNA package and assembles around it has remained an elusive one to solve. In this review, we will summarize what is known about the alphavirus capsid protein, the packaging signal, and their roles in the mechanism of packaging and assembly. We will review the discovery of the packaging signal and how there is as much evidence for, as well as against, its requirement to specify packaging of the genomic RNA. Finally, we will compare this model with those of other viral systems including particular reference to a relatively new idea of RNA packaging based on the presence of multiple minimal packaging signals throughout the genome known as the two stage mechanism. This review will provide a basis for further investigating the fundamental ways of how RNA viruses are able to select their own cargo from the relative chaos that is the cytoplasm.
Topics: Alphavirus; Animals; Capsid Proteins; Humans; Models, Biological; Nucleocapsid; Virus Assembly; Virus Replication
PubMed: 29558394
DOI: 10.3390/v10030138 -
Current Opinion in Virology Feb 2018Alphaviruses are important human pathogens that cause diseases ranging from acute and chronic polyarthralgia to encephalitis. Transmitted by mosquito vectors,... (Review)
Review
Alphaviruses are important human pathogens that cause diseases ranging from acute and chronic polyarthralgia to encephalitis. Transmitted by mosquito vectors, alphaviruses have high potential for emergence and have initiated several recent epidemics. The innate immune response is critical for controlling the acute phase of alphavirus disease, and the induction of type I interferon (IFN) is essential in this response. In this review, we discuss our current understanding of innate host sensors that initiate antiviral responses following alphavirus infection, and the IFN-induced effector proteins that limit alphavirus replication and dissemination.
Topics: Alphavirus; Alphavirus Infections; Animals; Humans; Immunity, Innate; Interferon Type I; Mice; Toll-Like Receptors; Virus Replication
PubMed: 29175515
DOI: 10.1016/j.coviro.2017.11.006 -
Frontiers in Immunology 2022Alphaviruses contain many human and animal pathogens, such as CHIKV, SINV, and VEEV. Accumulating evidence indicates that innate immunity plays an important role in... (Review)
Review
Alphaviruses contain many human and animal pathogens, such as CHIKV, SINV, and VEEV. Accumulating evidence indicates that innate immunity plays an important role in response to alphaviruses infection. In parallel, alphaviruses have evolved many strategies to evade host antiviral innate immunity. In the current review, we focus on the underlying mechanisms employed by alphaviruses to evade cGAS-STING, IFN, transcriptional host shutoff, translational host shutoff, and RNAi. Dissecting the detailed antiviral immune evasion mechanisms by alphaviruses will enhance our understanding of the pathogenesis of alphaviruses and may provide more effective strategies to control alphaviruses infection.
Topics: Alphavirus; Alphavirus Infections; Animals; Antiviral Agents; Humans; Immune Evasion; Nucleotidyltransferases
PubMed: 36172361
DOI: 10.3389/fimmu.2022.1005586 -
The Journal of Clinical Investigation Jan 2023Alphaviruses are enveloped, insect-transmitted, positive-sense RNA viruses that infect humans and other animals and cause a range of clinical manifestations, including... (Review)
Review
Alphaviruses are enveloped, insect-transmitted, positive-sense RNA viruses that infect humans and other animals and cause a range of clinical manifestations, including arthritis, musculoskeletal disease, meningitis, encephalitis, and death. Over the past four years, aided by CRISPR/Cas9-based genetic screening approaches, intensive research efforts have focused on identifying entry receptors for alphaviruses to better understand the basis for cellular and species tropism. Herein, we review approaches to alphavirus receptor identification and how these were used for discovery. The identification of new receptors advances our understanding of viral pathogenesis, tropism, and evolution and is expected to contribute to the development of novel strategies for prevention and treatment of alphavirus infection.
Topics: Animals; Humans; Alphavirus Infections; Alphavirus
PubMed: 36647825
DOI: 10.1172/JCI165307 -
Nature Reviews. Microbiology Jun 2023Alphaviruses are arthropod-transmitted RNA viruses that cause epidemics of human infection and disease on a global scale. These viruses are classified as either... (Review)
Review
Alphaviruses are arthropod-transmitted RNA viruses that cause epidemics of human infection and disease on a global scale. These viruses are classified as either arthritogenic or encephalitic based on their genetic relatedness and the clinical syndromes they cause. Although there are currently no approved therapeutics or vaccines against alphaviruses, passive transfer of monoclonal antibodies confers protection in animal models. This Review highlights recent advances in our understanding of the host factors required for alphavirus entry, the mechanisms of action by which protective antibodies inhibit different steps in the alphavirus infection cycle and candidate alphavirus vaccines currently under clinical evaluation that focus on humoral immunity. A comprehensive understanding of alphavirus entry and antibody-mediated protection may inform the development of new classes of countermeasures for these emerging viruses.
Topics: Animals; Humans; Alphavirus; Alphavirus Infections; Antibodies, Monoclonal
PubMed: 36474012
DOI: 10.1038/s41579-022-00825-7 -
PLoS Pathogens Oct 2020Alphaviruses cause severe human illnesses including persistent arthritis and fatal encephalitis. As alphavirus entry into target cells is the first step in infection,... (Review)
Review
Alphaviruses cause severe human illnesses including persistent arthritis and fatal encephalitis. As alphavirus entry into target cells is the first step in infection, intensive research efforts have focused on elucidating aspects of this pathway, including attachment, internalization, and fusion. Herein, we review recent developments in the molecular understanding of alphavirus entry both in vitro and in vivo and how these advances might enable the design of therapeutics targeting this critical step in the alphavirus life cycle.
Topics: Alphavirus; Alphavirus Infections; Animals; Host-Pathogen Interactions; Humans; Virus Internalization; Virus Replication
PubMed: 33091085
DOI: 10.1371/journal.ppat.1008876