Caracterização dos orthobunyavirus do grupo C: indução de genes estimulados por interferons pelo vírus caraparu in vitro e sequenciamento parcial do vírus APEU

Abstract

Group C Orthobunyaviruses - Caraparu virus (CARV) and Apeu virus (APEUV) were isolated in Brazilian Amazonia during the 1950s. These viruses could affect human being causing a disease characterized by high fever, muscular pain and photophobia during 4-5 days. Although group C viruses show a potential to emerge as human pathogens, studies with this viral family, especially involving this serogroup, are very rare and its biological and molecular characteristics are even less known. The interferons (IFNs) are a cytokine family important in the innate immune system regulation. IFNs play an essential role as first line defense against viral infections. The study of their interaction with these viruses can bring information about the innate immunity stimulated by them. Cells infected by viruses, synthesize and release type I and type III IFNs which signalize their neighbor cells to express antiviral proteins to moderate viral multiplication and their spreading. In this study, we have evaluated biological characteristics of CARV and molecular characteristics of APEUV, and we have shown some important aspects ofthem. CARV presented, in vitro, sensibility to type I and type III IFNs in Vero cells. The inhibition promoted by type I IFN (IFN) was greater than the inhibition promoted by type III (IFN). The associated use of type I and type III IFNs shows that there is no enhancement of one IFN type activity by the presence of a different IFN type. It was shown that CARV is able to induce ISGs expression, MxA and IRF7, and IFN-, 1 and 2/3 in infected A549 cells. Thus, we could conclude that, CARV presents in vitro sensibility to type I and type III IFNs, and it is able to induce IFN and ISGs expression in infected A549 cells. Thus, we can deduce that the IFN system has an important role in the innate immunity developed against this virus. As part of molecular characterization of APEUV, partial nucleotide sequences of the S segment from 4 plaque-purified APEUV clones and from the non-cloned APEUV (original virus stock) were obtained and compared to the sequence APEUV-CL5 (MAGALHÃES, 2008) revealing that all of the sequences were identical. These results suggest that the sample of APEUV used in this work is homogeneous and that this S segment variant is representative of the original viruspopulation.