RESUMO
The destruction of CD4(+) T cells and eventual induction of immunodeficiency is a hallmark of the human immunodeficiency virus type 1 infection (HIV-1). However, the mechanism of this destruction remains unresolved. Several auxiliary proteins have been proposed to play a role in this aspect of HIV pathogenesis including a 14 kDa protein named viral protein R (Vpr). Vpr has been implicated in the regulation of various cellular functions including apoptosis, cell cycle arrest, differentiation, and immune suppression. However, the mechanism(s) involved in Vpr-mediated apoptosis remains unresolved, and several proposed mechanisms for these effects are under investigation. In this review, we discuss the possibility that some of these proposed pathways might converge to modulate Vpr's behavior. Further, we also discuss caveats and future directions for investigation of the interesting biology of this HIV accessory gene.
Assuntos
Apoptose , Linfócitos T CD4-Positivos/virologia , Produtos do Gene vpr/fisiologia , HIV-1/fisiologia , Proteínas Adaptadoras de Transdução de Sinal , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Complexo do Signalossomo COP9 , Proteínas de Transporte/fisiologia , Fatores de Iniciação em Eucariotos/fisiologia , Produtos do Gene vpr/antagonistas & inibidores , Produtos do Gene vpr/farmacologia , Proteínas de Choque Térmico HSP70/farmacologia , Humanos , Membranas Intracelulares/efeitos dos fármacos , Potenciais da Membrana/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Complexos Multiproteicos/fisiologia , Peptídeo Hidrolases/fisiologia , Receptores de Glucocorticoides/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Produtos do Gene vpr do Vírus da Imunodeficiência HumanaRESUMO
West Nile virus (WNV) is a vectorborne pathogen that induces brain inflammation and death. Recently, confirmed cases of infection and deaths have occurred in the United States Mid-Atlantic region. In this study, a DNA vaccine encoding the WNV capsid protein was constructed, and the in vivo immune responses generated were investigated in DNA vaccine-immunized mice. Antigen-specific humoral and cellular immune responses were observed, including a potent induction of antigen-specific Th1 and cytotoxic T lymphocyte responses. Strong induction of Th1-type immune responses included high levels of antigen-specific elaboration of the Th1-type cytokines interferon-gamma and interleukin-2 and beta-chemokines RANTES (regulated upon activation, normal T cell-expressed and secreted) and macrophage inflammatory protein-1beta. Dramatic infiltration of CD4 and CD8 T cells and macrophages also was observed at the muscle injection site. These results support the potential utility of this method as a tool for developing immunization strategies for WNV and other emerging pathogens.