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The Journal of General Virology Aug 2021Human pathogens belonging to the genus, in the family, are transmitted primarily by mosquitoes. The signs and symptoms associated with these viruses include fever and... (Review)
Review
Human pathogens belonging to the genus, in the family, are transmitted primarily by mosquitoes. The signs and symptoms associated with these viruses include fever and polyarthralgia, defined as joint pain and inflammation, as well as encephalitis. In the last decade, our understanding of the interactions between members of the alphavirus genus and the human host has increased due to the re-appearance of the chikungunya virus (CHIKV) in Asia and Europe, as well as its emergence in the Americas. Alphaviruses affect host immunity through cytokines and the interferon response. Understanding alphavirus interactions with both the innate immune system as well as the various cells in the adaptive immune systems is critical to developing effective therapeutics. In this review, we summarize the latest research on alphavirus-host cell interactions, underlying infection mechanisms, and possible treatments.
Topics: Alphavirus; Alphavirus Infections; Animals; Humans; Viral Vaccines
PubMed: 34435944
DOI: 10.1099/jgv.0.001644 -
Antiviral Research Jan 2023The alphaviruses are a widely distributed group of positive-sense, single stranded, RNA viruses. These viruses are largely arthropod-borne and can be found on all... (Review)
Review
The alphaviruses are a widely distributed group of positive-sense, single stranded, RNA viruses. These viruses are largely arthropod-borne and can be found on all populated continents. These viruses cause significant human disease, and recently have begun to spread into new populations, such as the expansion of Chikungunya virus into southern Europe and the Caribbean, where it has established itself as endemic. The study of alphaviruses is an active and expanding field, due to their impacts on human health, their effects on agriculture, and the threat that some pose as potential agents of biological warfare and terrorism. In this systematic review we will summarize both historic knowledge in the field as well as recently published data that has potential to shift current theories in how alphaviruses are able to function. This review is comprehensive, covering all parts of the alphaviral life cycle as well as a brief overview of their pathology and the current state of research in regards to vaccines and therapeutics for alphaviral disease.
Topics: Humans; Antiviral Agents; Virus Replication; Chikungunya virus; Alphavirus Infections; Caribbean Region
PubMed: 36436722
DOI: 10.1016/j.antiviral.2022.105476 -
Seminars in Cell & Developmental Biology Mar 2021Alphaviruses such as chikungunya and western equine encephalitis viruses are important human pathogens transmitted by mosquitoes that have recently caused large epidemic... (Review)
Review
Alphaviruses such as chikungunya and western equine encephalitis viruses are important human pathogens transmitted by mosquitoes that have recently caused large epidemic and epizootic outbreaks. The epidemic potential of alphaviruses is often related to enhanced mosquito transmission. Tissue barriers and antiviral responses impose bottlenecks to viral populations in mosquitoes. Substitutions in the envelope proteins and the presence of repeated sequence elements (RSEs) in the 3'UTR of epidemic viruses were proposed to be specifically associated to efficient replication in mosquito vectors. Here, we discuss the molecular mechanisms that originated RSEs, the evolutionary forces that shape the 3'UTR of alphaviruses, and the significance of RSEs for mosquito transmission. Finally, the presence of RSEs in the 3'UTR of viral genomes appears as evolutionary trait associated to mosquito adaptation and emerges as a common feature among viruses from the alphavirus and flavivirus genera.
Topics: 3' Untranslated Regions; Alphavirus Infections; Animals; Chikungunya virus; Culicidae; Encephalitis Virus, Western Equine; Flavivirus; Flavivirus Infections; Gene Expression Regulation; Genome, Viral; Humans; Microsatellite Repeats; Mosquito Vectors; Phylogeny; Signal Transduction; Viral Envelope Proteins; Virus Replication
PubMed: 32665176
DOI: 10.1016/j.semcdb.2020.07.006 -
Viruses Aug 2023Chikungunya virus (CHIKV), an alphavirus transmitted by mosquitoes, has experienced a recent re-emergence in various regions of the world, leading to large-scale...
Chikungunya virus (CHIKV), an alphavirus transmitted by mosquitoes, has experienced a recent re-emergence in various regions of the world, leading to large-scale outbreaks [...].
Topics: Animals; Chikungunya virus; Culicidae; Disease Outbreaks
PubMed: 37632110
DOI: 10.3390/v15081768 -
Cell Reports May 2023RNA interference (RNAi) is a well-established antiviral immunity. However, for mammalian somatic cells, antiviral RNAi becomes evident only when viral suppressors of...
RNA interference (RNAi) is a well-established antiviral immunity. However, for mammalian somatic cells, antiviral RNAi becomes evident only when viral suppressors of RNAi (VSRs) are disabled by mutations or VSR-targeting drugs, thereby limiting its scope as a mammalian immunity. We find that a wild-type alphavirus, Semliki Forest virus (SFV), triggers the Dicer-dependent production of virus-derived small interfering RNAs (vsiRNAs) in both mammalian somatic cells and adult mice. These SFV-vsiRNAs are located at a particular region within the 5' terminus of the SFV genome, Argonaute loaded, and active in conferring effective anti-SFV activity. Sindbis virus, another alphavirus, also induces vsiRNA production in mammalian somatic cells. Moreover, treatment with enoxacin, an RNAi enhancer, inhibits SFV replication dependent on RNAi response in vitro and in vivo and protects mice from SFV-induced neuropathogenesis and lethality. These findings show that alphaviruses trigger the production of active vsiRNA in mammalian somatic cells, highlighting the functional importance and therapeutic potential of antiviral RNAi in mammals.
Topics: Animals; Mice; RNA Interference; Antiviral Agents; Cell Line; RNA, Small Interfering; Semliki forest virus; Alphavirus Infections; Sindbis Virus; Mammals; Virus Replication
PubMed: 37104090
DOI: 10.1016/j.celrep.2023.112441 -
Viruses Jun 2016Alphaviruses cause debilitating disease in humans and animals and are transmitted by blood-feeding arthropods, typically mosquitoes. With a traditional focus on two... (Review)
Review
Alphaviruses cause debilitating disease in humans and animals and are transmitted by blood-feeding arthropods, typically mosquitoes. With a traditional focus on two models, Sindbis virus and Semliki Forest virus, alphavirus research has significantly intensified in the last decade partly due to the re-emergence and dramatic expansion of chikungunya virus in Asia, Europe, and the Americas. As a consequence, alphavirus-host interactions are now understood in much more molecular detail, and important novel mechanisms have been elucidated. It has become clear that alphaviruses not only cause a general host shut-off in infected vertebrate cells, but also specifically suppress different host antiviral pathways using their viral nonstructural proteins, nsP2 and nsP3. Here we review the current state of the art of alphavirus host cell shut-off of viral transcription and translation, and describe recent insights in viral subversion of interferon induction and signaling, the unfolded protein response, and stress granule assembly.
Topics: Alphavirus; Alphavirus Infections; Animals; Host-Pathogen Interactions; Humans; Immune Evasion; Immunity, Innate; Viral Nonstructural Proteins; Virulence Factors
PubMed: 27294951
DOI: 10.3390/v8060166 -
Nature Communications Jan 2024Members of the low-density lipoprotein receptor (LDLR) family, including LDLRAD3, VLDLR, and ApoER2, were recently described as entry factors for different alphaviruses....
Members of the low-density lipoprotein receptor (LDLR) family, including LDLRAD3, VLDLR, and ApoER2, were recently described as entry factors for different alphaviruses. However, based on studies with gene edited cells and knockout mice, blockade or abrogation of these receptors does not fully inhibit alphavirus infection, indicating the existence of additional uncharacterized entry factors. Here, we perform a CRISPR-Cas9 genome-wide loss-of-function screen in mouse neuronal cells with a chimeric alphavirus expressing the Eastern equine encephalitis virus (EEEV) structural proteins and identify LDLR as a candidate receptor. Expression of LDLR on the surface of neuronal or non-neuronal cells facilitates binding and infection of EEEV, Western equine encephalitis virus, and Semliki Forest virus. Domain mapping and binding studies reveal a low-affinity interaction with LA domain 3 (LA3) that can be enhanced by concatenation of LA3 repeats. Soluble decoy proteins with multiple LA3 repeats inhibit EEEV infection in cell culture and in mice. Our results establish LDLR as a low-affinity receptor for multiple alphaviruses and highlight a possible path for developing inhibitors that could mitigate infection and disease.
Topics: Horses; Animals; Mice; Alphavirus; Encephalitis Virus, Eastern Equine; Alphavirus Infections; Semliki forest virus; Lipoproteins, LDL
PubMed: 38172096
DOI: 10.1038/s41467-023-44624-x -
Viruses Jan 2022Alphaviruses () are arthropod-borne viruses responsible for several emerging diseases, maintained in nature through transmission between hematophagous arthropod vectors...
Alphaviruses () are arthropod-borne viruses responsible for several emerging diseases, maintained in nature through transmission between hematophagous arthropod vectors and susceptible vertebrate hosts. Although bats harbor many species of viruses, their role as reservoir hosts in emergent zoonoses has been verified only in a few cases. With bats being the second most diverse order of mammals, their implication in arbovirus infections needs to be elucidated. Reports on arbovirus infections in bats are scarce, especially in South American indigenous species. In this work, we report the genomic detection and identification of two different alphaviruses in oral swabs from bats captured in Northern Uruguay. Phylogenetic analysis identified Río Negro virus (RNV) in two different species: ( = 6) and spp. ( = 1) and eastern equine encephalitis virus (EEEV) in spp. ( = 2). Previous studies of our group identified RNV and EEEV in mosquitoes and horse serology, suggesting that they may be circulating in enzootic cycles in our country. Our findings reveal that bats can be infected by these arboviruses and that chiropterans could participate in the viral natural cycle as virus amplifiers or dead-end hosts. Further studies are warranted to elucidate the role of these mammals in the biological cycle of these alphaviruses in Uruguay.
Topics: Alphavirus; Alphavirus Infections; Animals; Arbovirus Infections; Arboviruses; Chiroptera; Encephalitis Virus, Eastern Equine; Phylogeny; Uruguay
PubMed: 35215862
DOI: 10.3390/v14020269 -
Viruses Jan 2023Eastern (EEEV), Venezuelan (VEEV), and western equine encephalitis viruses (WEEV) are members of the genus , family . Typically spread by mosquitoes, EEEV, VEEV, and... (Review)
Review
Eastern (EEEV), Venezuelan (VEEV), and western equine encephalitis viruses (WEEV) are members of the genus , family . Typically spread by mosquitoes, EEEV, VEEV, and WEEV induce febrile illness that may develop into more severe encephalitic disease, resulting in myriad severe neurologic sequelae for which there are no vaccines or therapeutics. Here, we summarize the clinical neurologic findings and sequelae induced by these three encephalitic viruses and describe the various animal models available to study them. We emphasize the crucial need for the development of advanced animal modeling combined with the use of telemetry, behavioral testing, and neuroimaging to facilitate a detailed mechanistic understanding of these encephalitic signs and sequelae. Through the use of these systems, much-needed therapeutics and vaccines can be developed.
Topics: Animals; Horses; Alphavirus; Encephalitis; Alphavirus Infections; Encephalitis Virus, Western Equine; Disease Progression; Models, Animal
PubMed: 36851596
DOI: 10.3390/v15020382 -
Viruses Feb 2018Alphaviruses are arthropod-borne viruses and are predominantly transmitted via mosquito vectors. This vector preference by alphaviruses raises the important question of... (Review)
Review
Alphaviruses are arthropod-borne viruses and are predominantly transmitted via mosquito vectors. This vector preference by alphaviruses raises the important question of the determinants that contribute to vector competence. There are several tissue barriers of the mosquito that the virus must overcome in order to establish a productive infection. Of importance are the midgut, basal lamina and the salivary glands. Infection of the salivary glands is crucial for virus transmission during the mosquito's subsequent bloodfeed. Other factors that may contribute to vector competence include the microflora and parasites present in the mosquito, environmental conditions, the molecular determinants of the virus to adapt to the vector, as well as the effect of co-infection with other viruses. Though mosquito innate immunity is a contributing factor to vector competence, it will not be discussed in this review. Detailed understanding of these factors will be instrumental in minimising transmission of alphaviral diseases.
Topics: Alphavirus; Alphavirus Infections; Animals; Coinfection; Culicidae; Humans; Mosquito Vectors; Mutation; RNA, Viral
PubMed: 29443908
DOI: 10.3390/v10020084