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Emerging Microbes & Infections Sep 2018Mayaro virus (MAYV), an enveloped RNA virus, belongs to the Togaviridae family and Alphavirus genus. This arthropod-borne virus (Arbovirus) is similar to Chikungunya... (Review)
Review
Mayaro virus (MAYV), an enveloped RNA virus, belongs to the Togaviridae family and Alphavirus genus. This arthropod-borne virus (Arbovirus) is similar to Chikungunya (CHIKV), Dengue (DENV), and Zika virus (ZIKV). The term "ChikDenMaZika syndrome" has been coined for clinically suspected arboviruses, which have arisen as a consequence of the high viral burden, viral co-infection, and co-circulation in South America. In most cases, MAYV disease is nonspecific, mild, and self-limited. Fever, arthralgia, and maculopapular rash are among the most common symptoms described, being largely indistinguishable from those caused by other arboviruses. However, severe manifestations of the infection have been reported, such as chronic polyarthritis, neurological complications, hemorrhage, myocarditis, and even death. Currently, there are no specific commercial tools for the diagnosis of MAYV, and the use of serological methods can be affected by cross-reactivity and the window period. A diagnosis based on clinical and epidemiological data alone is still premature. Therefore, new entomological research is warranted, and new highly specific molecular diagnostic methods should be developed. This comprehensive review is intended to encourage public health authorities and scientific communities to actively work on diagnosing, preventing, and treating MAYV infection.
Topics: Alphavirus; Alphavirus Infections; Animals; Communicable Diseases, Emerging; Humans; South America
PubMed: 30254258
DOI: 10.1038/s41426-018-0163-5 -
Advances in Virus Research 2017The Bunyavirales Order encompasses nine families of enveloped viruses containing a single-stranded negative-sense RNA genome divided into three segments. The small (S)... (Review)
Review
The Bunyavirales Order encompasses nine families of enveloped viruses containing a single-stranded negative-sense RNA genome divided into three segments. The small (S) and large (L) segments encode proteins participating in genome replication in the infected cell cytoplasm. The middle (M) segment encodes the viral glycoproteins Gn and Gc, which are derived from a precursor polyprotein by host cell proteases. Entry studies are available only for a few viruses in the Order, and in each case they were shown to enter cells via receptor-mediated endocytosis. The acidic endosomal pH triggers the fusion of the viral envelope with the membrane of an endosome. Structural studies on two members of this Order, the phleboviruses and the hantaviruses, have shown that the membrane fusion protein Gc displays a class II fusion protein fold and is homologous to its counterparts in flaviviruses and alphaviruses, which are positive-sense, single-stranded RNA viruses. We analyze here recent data on the structure and function of the structure of the phlebovirus Gc and hantavirus Gn and Gc glycoproteins, and extrapolate common features identified in the amino acid sequences to understand also the structure and function of their counterparts in other families of the Bunyavirales Order. Our analysis also identified clear structural homology between the hantavirus Gn and alphavirus E2 glycoproteins, which make a heterodimer with the corresponding fusion proteins Gc and E1, respectively, revealing that not only the fusion protein has been conserved across viral families.
Topics: Alphavirus; Animals; Biological Evolution; Bunyaviridae Infections; Endosomes; Genome, Viral; Orthohantavirus; Humans; Models, Molecular; Phlebovirus; Phylogeny; Protein Folding; RNA, Viral; Structural Homology, Protein; Viral Fusion Proteins; Virus Internalization
PubMed: 28433053
DOI: 10.1016/bs.aivir.2017.02.002 -
Mammalian Genome : Official Journal of... Aug 2018Alphaviruses, members of the positive-sense, single-stranded RNA virus family Togaviridae, represent a re-emerging public health concern worldwide as mosquito vectors... (Review)
Review
Alphaviruses, members of the positive-sense, single-stranded RNA virus family Togaviridae, represent a re-emerging public health concern worldwide as mosquito vectors expand into new geographic ranges. Members of the alphavirus genus tend to induce clinical disease characterized by rash, arthralgia, and arthritis (chikungunya virus, Ross River virus, and Semliki Forest virus) or encephalomyelitis (eastern equine encephalitis virus, western equine encephalitis virus, and Venezuelan equine encephalitis virus), though some patients who recover from the initial acute illness may develop long-term sequelae, regardless of the specific infecting virus. Studies examining the natural disease course in humans and experimental infection in cell culture and animal models reveal that host genetics play a major role in influencing susceptibility to infection and severity of clinical disease. Genome-wide genetic screens, including loss of function screens, microarrays, RNA-sequencing, and candidate gene studies, have further elucidated the role host genetics play in the response to virus infection, with the immune response being found in particular to majorly influence the outcome. This review describes the current knowledge of the mechanisms by which host genetic factors influence alphavirus pathogenesis and discusses emerging technologies that are poised to increase our understanding of the complex interplay between viral and host genetics on disease susceptibility and clinical outcome.
Topics: Alphavirus; Alphavirus Infections; Animals; Arthropods; Biomarkers; Disease Models, Animal; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Host-Pathogen Interactions; Humans
PubMed: 30151711
DOI: 10.1007/s00335-018-9776-1 -
Virus Research Apr 2017Alphaviruses are typically arthropod-borne, and many are important pathogens such as chikungunya virus. Alphaviruses encode four nonstructural proteins (nsP1-4),... (Review)
Review
Alphaviruses are typically arthropod-borne, and many are important pathogens such as chikungunya virus. Alphaviruses encode four nonstructural proteins (nsP1-4), initially produced as a polyprotein P1234. nsP4 is the core RNA-dependent RNA polymerase but all four nsPs are required for RNA synthesis. The early replication complex (RC) formed by the polyprotein P123 and nsP4 synthesizes minus RNA strands, and the late RC composed of fully processed nsP1-nsP4 is responsible for the production of genomic and subgenomic plus strands. Different parts of nsP4 recognize the promoters for minus and plus strands but the binding also requires the other nsPs. The alphavirus polymerase has been purified and is capable of de novo RNA synthesis only in the presence of the other nsPs. The purified nsP4 also has terminal adenylyltransferase activity, which may generate the poly(A) tail at the 3' end of the genome. Membrane association of the nsPs is vital for replication, and alphaviruses induce membrane invaginations called spherules, which form a microenvironment for RNA synthesis by concentrating replication components and protecting double-stranded RNA intermediates. The RCs isolated as crude membrane preparations are active in RNA synthesis in vitro, but high-resolution structure of the RC has not been achieved, and thus the arrangement of viral and possible host components remains unknown. For some alphaviruses, Ras-GTPase-activating protein (Src-homology 3 (SH3) domain)-binding proteins (G3BPs) and amphiphysins have been shown to be essential for RNA replication and are present in the RCs. Host factors offer an additional target for antivirals, as only few alphavirus polymerase inhibitors have been described.
Topics: Alphavirus; Cell Membrane; Promoter Regions, Genetic; Protein Binding; RNA, Viral; RNA-Dependent RNA Polymerase; Viral Nonstructural Proteins; Virus Replication
PubMed: 28104453
DOI: 10.1016/j.virusres.2017.01.007 -
Best Practice & Research. Clinical... Aug 2020Arboviruses (ARthropods BOrne VIRUSES) are disease-causing viruses transmitted through the bite of hematophagous arthropods, such as mosquitoes and ticks. Among these,... (Review)
Review
Arboviruses (ARthropods BOrne VIRUSES) are disease-causing viruses transmitted through the bite of hematophagous arthropods, such as mosquitoes and ticks. Among these, the alphavirus, genus of the Togaviridae family, is considered the most arthritogenic species, responsible for diseases such as chikungunya fever (CHIK), O'nyong-nyong virus fever, Ross River virus disease, Barmah Forest virus disease, Sindbis virus disease, and Mayaro fever. These arboviral diseases, especially CHIK, have impacted public health in recent decades, leading to devastating epidemics, particularly in developing countries, due to their high potential for chronicity, functional impairment, and great impact on the quality of life. In a similar way, chronic musculoskeletal symptoms have been described in all alphavirus infections. However, CHIK is the best studied. The purpose of this article is to review physiopathology, clinical manifestations, diagnosis, and treatment of alphaviruses, focusing on CHIK and chronic evolution of musculoskeletal symptoms.
Topics: Alphavirus; Alphavirus Infections; Animals; Arboviruses; Fever; Humans; Musculoskeletal Diseases; Quality of Life
PubMed: 32312678
DOI: 10.1016/j.berh.2020.101502 -
The Journal of General Virology Feb 2015Part of the Togaviridae family, alphaviruses are arthropod-borne viruses that are widely distributed throughout the globe. Alphaviruses are able to infect a variety of... (Review)
Review
Part of the Togaviridae family, alphaviruses are arthropod-borne viruses that are widely distributed throughout the globe. Alphaviruses are able to infect a variety of vertebrate hosts, but in humans, infection can result in extensive morbidity and mortality. Symptomatic infection can manifest as fever, an erythematous rash and/or significant inflammatory pathologies such as arthritis and encephalitis. Recent overwhelming outbreaks of alphaviral disease have highlighted the void in our understanding of alphavirus pathogenesis and the re-emergence of alphaviruses has given new impetus to anti-alphaviral drug design. In this review, the development of viable mouse models of Old Word and New World alphaviruses is examined. How mouse models that best replicate human disease have been used to elucidate the immunopathology of alphavirus pathogenesis and trial novel therapeutic discoveries is also discussed.
Topics: Alphavirus; Alphavirus Infections; Animals; Disease Models, Animal; Host-Pathogen Interactions; Humans; Mice
PubMed: 25351726
DOI: 10.1099/vir.0.071282-0 -
Cell Reports May 2023Arboviruses are public health threats that cause explosive outbreaks. Major determinants of arbovirus transmission, geographic spread, and pathogenesis are the magnitude...
Arboviruses are public health threats that cause explosive outbreaks. Major determinants of arbovirus transmission, geographic spread, and pathogenesis are the magnitude and duration of viremia in vertebrate hosts. Previously, we determined that multiple alphaviruses are cleared efficiently from murine circulation by the scavenger receptor MARCO (Macrophage receptor with collagenous structure). Here, we define biochemical features on chikungunya (CHIKV), o'nyong 'nyong (ONNV), and Ross River (RRV) viruses required for MARCO-dependent clearance in vivo. In vitro, MARCO expression promotes binding and internalization of CHIKV, ONNV, and RRV via the scavenger receptor cysteine-rich (SRCR) domain. Furthermore, we observe species-specific effects of the MARCO SRCR domain on CHIKV internalization, where those from known amplification hosts fail to promote CHIKV internalization. Consistent with this observation, CHIKV is inefficiently cleared from the circulation of rhesus macaques in contrast with mice. These findings suggest a role for MARCO in determining whether a vertebrate serves as an amplification or dead-end host following CHIKV infection.
Topics: Animals; Mice; Chikungunya virus; Viremia; Macaca mulatta; Chikungunya Fever; Disease Outbreaks; Receptors, Immunologic
PubMed: 37083332
DOI: 10.1016/j.celrep.2023.112418 -
Advances in Virus Research 2021Alphaviruses are positive-strand RNA viruses, typically transmitted by mosquitoes between vertebrate hosts. They encode four essential replication proteins, the... (Review)
Review
Alphaviruses are positive-strand RNA viruses, typically transmitted by mosquitoes between vertebrate hosts. They encode four essential replication proteins, the non-structural proteins nsP1-4, which possess the enzymatic activities of RNA capping, RNA helicase, site-specific protease, ADP-ribosyl removal and RNA polymerase. Alphaviruses have been key models in the study of membrane-associated RNA replication, which is a conserved feature among the positive-strand RNA viruses of animals and plants. We review new structural and functional information on the nsPs and their interaction with host proteins and membranes, as well as with viral RNA sequences. The dodecameric ring structure of nsP1 is likely to be one of the evolutionary innovations that facilitated the success of the progenitors of current positive-strand RNA viruses.
Topics: Alphavirus; Animals; RNA, Viral; Vertebrates; Viral Nonstructural Proteins; Virus Replication
PubMed: 34663497
DOI: 10.1016/bs.aivir.2021.07.003 -
Journal of Virology Jun 2018Alphaviruses are transmitted to humans via bites of infected mosquitoes. Although alphaviruses have caused a wide range of outbreaks and crippling disease, the... (Review)
Review
Alphaviruses are transmitted to humans via bites of infected mosquitoes. Although alphaviruses have caused a wide range of outbreaks and crippling disease, the availability of licensed vaccines or antiviral therapies remains limited. Mosquito vectors such as and are the main culprits in the transmission of alphaviruses. This review explores how mosquito saliva may promote alphavirus infection. Identifying the roles of mosquito-derived factors in alphavirus pathogenesis will generate novel tools to circumvent and control mosquito-borne alphavirus infections in humans.
Topics: Adaptive Immunity; Aedes; Alphavirus; Alphavirus Infections; Animals; Culex; Humans; Immunity, Innate; Immunosuppression Therapy; Saliva; Skin
PubMed: 29593049
DOI: 10.1128/JVI.01004-17 -
International Review of Cell and... 2023Alphaviruses have frequently been engineered for cancer therapy, cancer immunotherapy, and cancer vaccine development. As members of self-replicating RNA viruses,...
Alphaviruses have frequently been engineered for cancer therapy, cancer immunotherapy, and cancer vaccine development. As members of self-replicating RNA viruses, alphaviruses provide high levels of transgene expression through efficient self-amplifying of their RNA genome in host cells. Alphavirus vectors can be used as recombinant viral particles or oncolytic viruses. Alternatively, either naked or nanoparticle-encapsulated RNA and DNA replicons can be utilized. In the context of cancer prevention and treatment, antitumor, cytotoxic and suicide genes have been expressed from alphavirus vectors to provide tumor regression and tumor eradication. Moreover, immunostimulatory genes such as cytokines and chemokines have been used for cancer immunotherapy approaches. Expression of tumor antigens has been applied for cancer vaccine development. Alphavirus vectors has demonstrated tumor regression and even cure in various preclinical animal models. Immunization has elicited strong immune responses and showed protection against challenges with tumor cells in animal models. Several clinical trials have confirmed good safety and tolerability of alphaviruses in cancer patients although therapeutic efficacy will still require optimization.
Topics: Animals; Alphavirus; Genetic Vectors; Immunotherapy; RNA; Neoplasms; Cancer Vaccines
PubMed: 37541722
DOI: 10.1016/bs.ircmb.2023.03.011