Zoonotic Vaccinia Viruses Belonging to Different Genetic Clades Exhibit Immunomodulation Abilities That Are Proportional to Their Pathogenic Potential

Abstract BackgroundThe Vaccinia virus (VACV) isolates, Guarani P1 virus (GP1V) and Passatempo virus (PSTV), were isolated from zoonotic outbreaks in Brazil and belong to two different VACV clades, as defined by biological aspects that include virulence in mice and phylogenetic analysis. Considering that information about how vaccinia viruses from different groups elicit immune responses in animals is scarce, we investigated such responses in mice infected by GP1V (group 2) or PSTV (group 1) using VACV Western Reserve strain (WR) as control. MethodsThe severity of the infections was evaluated in BALB/c mice considering diverse clinical signs and defined scores, and the immune responses triggered by GP1V and PSTV infections were analysed by immune cell phenotyping and intra-cytoplasmic cytokines detection. ResultsInfected mice showed significant weight loss and developed spleen lesions as well as liver and lung damage. Mice infected with PSTV, however, developed only moderate clinical signs. We detected a reduction of total lymphocytes (CD3+), macrophages (CD14+) and NK cells (CD3-CD49+) in animals infected with VACV-WR or GP1V. VACV-WR was able to significantly downmodulate cell immune responses upon mice infection, and GP1V-infected animals also showed intense downmodulation in cell responses. Contrarily, PSTV presented little ability to downmodulate mice immune responses. ConclusionsOur results suggest that VACV immunomodulation in vivo is clade-related and is proportional to the strain virulence upon infection. Our data corroborate the classification of the different Brazilian VACV isolates in clades 1 and 2, taking into account not only phylogenetic criteria, but also clinical and immunological data.