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Caracteriza??o gen?tica do v?rus Chikungunya circulante no Estado do Rio Grande do NortePereira, Hannaly Wana Bezerra 27 February 2018 (has links)
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Previous issue date: 2018-02-27 / A febre Chikungunya ? uma s?ndrome febril com grave artralgia debilitante, podendo evoluir para casos at?picos, como manifesta??es neurol?gicas e mucocut?neas. Geralmente ? transmitida por mosquitos do g?nero Aedes. O agente etiol?gico ? o v?rus Chikungunya (CHIKV) que pertence ? fam?lia Togaviridae e ao g?nero Alphavirus. At? pouco tempo essa doen?a era negligenciada no Brasil, por?m com o surto epid?mico que houve no ano de 2016, essa arbovirose se tornou um desafio para a sa?de p?blica. O objetivo do presente estudo foi realizar a caracteriza??o gen?tica do CHIKV identificado no Estado do Rio Grande do Norte (RN), no bi?nio 2016-2017. Um total de 10 amostras de soro, l?quor ou conte?do de ves?culas-bolhosas foram analisadas pela metodologia de qRT-PCR para detec??o do CHIKV e todas se apresentaram positivas. Foi realizada a filogenia e a caracteriza??o gen?tica do v?rus, por meio do sequenciamento da regi?o codificadora da poliprote?na estrutural, com posterior an?lise da estrutura da prote?na por meio da modelagem. A an?lise filogen?tica indicou que o gen?tipo circulante no Estado do Rio Grande do Norte ? o Leste-Centro-Sul Africano II (ECSA II). A compara??o entre as sequencias dos CHIKV deste estudo com aquelas de seu ancestral da linhagem ECSA II identificado em Uganda em 1982 (GenBank: HM045812) revelou a presen?a de 21 muta??es n?o sin?nimas. O sequenciamento dos CHIKV do soro e do l?quor de um mesmo paciente revelou duas muta??es n?o sin?nimas potencialmente associadas a neurovirul?ncia viral: N606K e P677L. Adicionalmente, a an?lise da modelagem de prote?nas mostrou que o v?rus circulante no Rio Grande do Norte n?o apresenta a muta??o na posi??o A226V, que determina uma maior infectividade do v?rus para o Aedes albopictus. Em conclus?o, esse estudo revela a origem do CHIKV circulante no Estado do Rio Grande do Norte e poss?veis marcadores de neurovirul?ncia viral, informa??es ?teis para compreender a evolu??o viral e a patog?nese da doen?a. / Chikungunya fever is a febrile syndrome with severe debilitating arthralgia, which may progress to atypical cases, such as neurological and mucocutaneous manifestations. It is usually transmitted by mosquitoes of the genus Aedes. The etiological agent is the Chikungunya virus (CHIKV) that belongs to the family Togaviridae and to the genus Alphavirus. Until recently this disease was neglected in Brazil, but with the epidemic outbreak that occurred in the year 2016, this arbovirose has become a challenge for public health. The objective of the present study was to perform the genetic characterization of the CHIKV identified in the State of Rio Grande do Norte (RN), in the biennium 2016-2017. A total of 10 serum samples, cerebrospinal fluid (CSF) or blister samples were analyzed by the qRT-PCR methodology for CHIKV detection and all were positive. Phylogeny and genetic characterization of the virus were performed by sequencing the coding region of the structural polyprotein, with subsequent analysis of the protein structure through modeling. Phylogenetic analysis indicated that the circulating genotype in the State of Rio Grande do Norte is East-Central-South-African II (ECSA II). The comparison between CHIKV sequenced in this study and its ancestor from ECSA II lineage identified in Uganda in 1982 (GenBank: HM045812) revealed the presence of 21 non-synonymous mutations. Sequencing of serum and CSF CHIKV from the same patient revealed two non-synonymous mutations potentially associated with viral neurovirulence: N606K and P677L. In addition, the analysis of the protein model showed the circulating non-RN virus has no mutation at position A226V which is the major part of virus infection for Aedes albopictus. In conclusion, this study reveals the origin of CHIKV circulating in the State of Rio Grande do Norte and possible markers of viral neurovirulence, useful information to understand the viral evolution and the pathogenesis of the disease.
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