SELECTIVE QUASI-SPECIES TRANSMISSION AFTER SYSTEMIC OR MUCOSAL EXPOSURE OF MACAQUES TO SIMIAN IMMUNODEFICIENCY VIRUS

Sexual transmission is the major cause of the AIDS epidemic. For the d evelopment of new antiviral and vaccine strategies, we therefore need to understand the mechanisms by which lentiviruses cross the mucosal b arrier and the subsequent pathogenic consequences. For this purpose, e xperimental approaches are greatly facilitated by the development of r elevant animal models. In this study, macaques were inoculated intrave nously, intrarectally, or intravaginally with a pathogenic cell-free i solate of SIVmac251. Patterns of virological and immunological events significantly differed between vaginally (transient viremia, late sero conversion] and intravenously or intrarectally inoculated monkeys (per sistent viremia and early seroconversion). Two weeks after infection, analysis of the env gene nucleotide sequences of proviruses recovered from PBMCs demonstrated that most of the differences were observed in the V1 loop, Three viral Variants were specifically associated with va ginal transmission, whereas no such selection was evidenced after intr avenous or intrarectal transmissions. These results are in favor of sp ecific mechanisms associated with vaginal transmission, implicating vi ral envelope structure. (C) 1998 Academic Press.