Human immunodeficiency virus (HIV) now causes more global mortality than any other single infectious agent and is the primary cause of death in Africa. Diagnostic assays and vaccines are central tools for addressing this problem. The effectiveness of these tools, however, may be limited by the genetic diversity of HIV. The forces that generate and maintain this diversity are incompletely understood. The proposed research investigates a potentially crucial natural mechanism for the introduction of novel HIV genetic diversity into the human population. We hypothesize that HIV genetic diversity emerges not only through the cross-species transmission of entire simian immunodeficiency virus (SIV) genomes, but also through the emergence of individual genes or genomic segments during recombination events between nonhuman lentiviruses and the fully human-adapted virus, HIV-1. While human hunters of nonhuman primates are at the front line of this interface, they have never, to our knowledge been systematically examined. This proposal includes four interrelated aims. First, we will assess the prevalence of HIV and HIV-related lentiviruses among hunters in Cameroon, using whole viral ELISAs and the Western Blot. Second, we will characterize positive isolates through the polymerase chain reaction (PCR) and heteroduplex mobility assay (HMA) at three independent genomic regions, which will reveal the broad phylogenetic relationships of these three regions of the HIV genome. Third, we will examine the detailed genetic mosaic structure of selected isolates in order to assess the genomic sites of recombination, using full-length genomic sequencing and phylogenetic analysis. Fourth, in the process of completing aims one through three, we will develop reagents from Cameroonian HIV isolates and adapt and field test an HMA appropriate for continued HIV surveillance in Cameroon. The proposed research will provide significant career development of the primary investigator through directed mentorship in the epidemiology, ecology, and molecular evolution of HIV and related viruses.