SELECTIVE AMPLIFICATION OF SIMIAN IMMUNODEFICIENCY VIRUS GENOTYPES AFTER INTRARECTAL INOCULATION OF RHESUS-MONKEYS

Animal models for sexual transmission of human immunodeficiency virus can define the influences of virus type, dose, and route of inoculatio n on infection and clinical outcome. We used an uncloned simian immuno deficiency virus stock (SIVmac) to inoculate cells in vitro and to ino culate rhesus monkeys by intravenous and intrarectal routes. The distr ibution of virus genotypes present in each of these infection examples was characterized by DNA sequence analysis of viral long terminal rep eats (LTRs). Our analysis of LTR sequences from in vitro and in vivo i nfections revealed three main genotypes: one genotype was observed onl y for in vitro infection, and two other genotypes were recovered only from infected animals. By comparing animals inoculated with high intra rectal doses of SIVmac and those inoculated with low doses, we demonst rated that unique subsets of the stock were selected after intrarectal infection. Our findings indicate that minor genotypes present in the stock cross the rectal mucosa and are amplified selectively to become prominent in peripheral blood mononuclear cells from acutely infected animals. Studies with a molecular recombinant of SIV and human immunod eficiency virus type 1 sequences, SHIV, showed that viral LTR sequence s do not undergo especially rapid sequence variation or rearrangement after intrarectal inoculation. The mucosal barrier exerts a significan t influence on infection and disease progression by reducing the effic iency of SIVmac infection and by permitting distinct, pathogenic genot ypes to become established in the host.