Mucosal Transmission and Induction of Simian AIDS by CCR5-Specific Simian/Human Immunodeficiency Virus SHIV SF162P3

Abstract

ABSTRACT Nonhuman primate models are increasingly used in the screening of candidate AIDS vaccine and immunization strategies for advancement to large-scale human trials. The predictive value of such macaque studies is largely dependent upon the fidelity of the model system in mimicking human immunodeficiency virus (HIV) type 1 infection in terms of viral transmission, replication, and pathogenesis. Herein, we describe the efficient mucosal transmission of a CCR5-specific chimeric simian/human immunodeficiency virus, SHIV SF162P3 . Female rhesus macaques were infected with SHIV SF162P3 after a single atraumatic application to the cervicovaginal mucosa. The disease course of SHIV SF162P3 -infected monkeys is similar and as varied as natural HIV infection in terms of viral replication, gradual loss of CD4 + peripheral blood mononuclear cells, and the development of simian AIDS-defining opportunistic infections. The SHIV SF162P3 /macaque model should facilitate direct preclinical assessment of HIV vaccine strategies in addition to antiviral compounds directed towards envelope target cell interactions. Furthermore, this controlled model provides the setting to investigate immunologic responses and putative host-specific susceptibility factors that alter viral transmission and subsequent disease progression.