Modelos de Infecção localizada em camundongos utilizando o Vaccinia virus: implicações para estudos de resposta imune do hospedeiro, terapêutica e variabilidade fenotípica destes vírus

Abstract

The family Poxviridae contains the largest DNA viruses that infect animals, which posses a wide range of genes dedicated to evasion of the host immune system. Among these members, the best known are the human pathogen Variola virus (VARV), and the zoonotic virus Vaccinia virus (VACV). VACV strains were used in the global smallpox eradication campaing, and besides that, other strains from the same species are responsible for outbreaks in Asia and Brazil. Infection with VACV, natural or by means of vaccination, are acquired through direct contact and may lead to complications due to uncontrolled viral replication in immunosupressed hosts. There is no treatment available yet and the vaccination is the only way to prevent these infections. Despite the relevance of VACV in public health, little is known about its biology and pathogenesis. This is because most of the studies have employed models of systemic disease in laboratory animals, such as the intranasal and intraperitoneal routes of infection. The localized models, on the other hand, most closely resemble the clinical and immunological aspects of VACV natural infection. The goals of this work were hence employ localized models of infection with VACV in mice to study the immune response to a primary infection, besides study the efficacy of a new drug in the treatment of these infections and evaluate if the genetic diversity of these viruses might affect their susceptibility to the treatment. The results obtained showed that both T and B cells are crucial for full protection upon VACV infection using the tail scarification route of infection. Furthermore, the TLR7 agonist Imiquimod is efficient to treat infections with wild and vaccine strains of VACV, but not with the prototype strain WR, using intradermic inoculation in mice. Genetic analysis showed that this different susceptibility might be due to polymorfisms located in viral genes responsible for host immune evasion. Together, these data provide important insights that would be helpful to construct a safer vaccine and to develop a new therapeutic drug to treat these zoonotic infections.