Caracterização dos isolados zoonóticos de vaccinia virus guarani p1 (gp1v) e passatempo (pstv) e avaliação de sua capacidade em modular vias de resposta do hospedeiro à infecção, in vivo e in vitro

Abstract

The family Poxviridae has notorious members known in the whole world due to their capacity of infect a great variaty of hosts, vertebrates and invertebrates, including humans. Poxviruses are divided into two subfamilies: Entomopoxvirinae, which includes poxviruses that infect insects, and Chordopoxvirinae, that contains poxviruses that infect vertebrates. The subfamily Chordopoxvirinae has twelve genera, and the Orthopoxvirus stands out among the most studied. It is estimated that members of the genus Orthopoxvirus circulate in the Brazilian wild environment for several decades or even more. Since 1999, the Vaccinia virus (VACV) has been associated to outbreaks involving humans and cattle, horses and other animals. Based on several studies conducted by Brazilian researchers, VACV isolates were separated into two groups: group 1 (less virulent in murine infection models) and group 2 (more virulent in murine infection models). This classification is due to biological properties of the isolates, such as virulence in BALB/c mice, infectivity in BSC-40 cells and presence or absence of a 18 nucleotide deletion in the gene encoding the viral hemagglutinin (HA or A26R) protein. In this project, the pathogenic profile in cell culture and in Balb/c mice, respectively, of the Brazilian isolates of VACV Guarani P1 virus (GP1V) and Passatempo virus (PSTV) were investigated, compared to VACV Western Reserve (VACV-WR). Precisely, we analysed the ability of GP1V and PSTV isolates to modulate the response to unfolded proteins (UPR) in the endoplasmic reticulum of infected cells. We also evaluated pathogenic aspects of these samples – such as their organic tropism – and the serologic and cross-protection profiles of the isolates induced by infection in Balb/c mice from the production of cross-neutralizing antibodies. In conclusion, GP1V has a virulence profile similar to WR, while PSTV exhibits a more moderate profile.