Autor(es): Nasar Farooq, Gorchakov Rodion V, Tesh Robert B, Weaver Scott C

Resumo: Most alphaviruses are mosquito-borne - exhibit a broad host range, infecting many different vertebrates, including birds, rodents, equids, humans, - nonhuman primates. This ability of most alphaviruses to infect arthropods - vertebrates is essential for their maintenance in nature. Recently, a new alphavirus, Eilat virus (EILV), was described, - in contrast to all other mosquito-borne viruses, it is unable to replicate in vertebrate cell lines. Investigations into the nature of its host range restriction showed the inability of genomic EILV RNA to replicate in vertebrate cells. Here, we investigated whether the EILV host range restriction is present at the entry level - further explored the viral factors responsible for the lack of genomic RNA replication. Utilizing Sindbis virus (SINV) - EILV chimeras, we show that the EILV vertebrate host range restriction is also manifested at the entry level. Furthermore, the EILV RNA replication restriction is independent of the 3' untranslated genome region (UTR). Complementation experiments with SINV suggested that RNA replication is restricted by the inability of the EILV nonstructural proteins to form functional replicative complexes. These data demonstrate that the EILV host range restriction is multigenic, involving at least one gene from both nonstructural protein (nsP) - structural protein (sP) open reading frames (ORFs). As EILV groups phylogenetically within the mosquito-borne virus clade of pathogenic alphaviruses, our findings have important evolutionary implications for arboviruses. Our work explores the nature of host range restriction of the first mosquito-only alphavirus," EILV. EILV is related to pathogenic mosquito-borne viruses (Eastern equine encephalitis virus [EEEV], Western equine encephalitis virus [WEEV], Venezuelan equine encephalitis virus [VEEV], - Chikungunya virus [CHIKV]) that cause severe disease in humans. Our data demonstrate that EILV is restricted both at entry - genomic RNA replication levels in vertebrate cells. These findings have important implications for arbovirus evolution - will help elucidate the viral factors responsible for the broad host range of pathogenic mosquito-borne alphaviruses, facilitate vaccine development, - inform potential strategies to reduce/prevent alphavirus transmission."

Imprenta: Journal of Virology, v. 89, n. 2, p. 1404-1418, 2015

Identificador do objeto digital: 10.1128/JVI.01856-14

Descritores: Chikungunya virus - Arbovirus ; Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - Genome ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - RNA ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Transmission ; Chikungunya virus - Vaccine ; Chikungunya virus - Immunology

Data de publicação: 2015

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