Early events of rectal transmission of Simian Immunodeficiency Virus

To better understand the early events of HIV rectal transmission, we studied the timing, location and the cell types of virus-infected cells in rhesus macaque model of HIV rectal transmission.  49 adult male Indian rhesus macaques were intrarectally inoculated with SIVmac251 (3.4 x10^4 TCID₅₀) and euthanized at various days post inoculation (0, 1, 2, 3, 4, 6 10, 12 day, 3 and 6 months PI). The tissues from over a dozen different anatomic sites were analyzed for the presence of SIV vRNA using qRT-PCR and in situ hybridization (ISH). At 3 and 4 dpi, SIV was only detected in the rectum and draining lymph nodes (LNs), but not in the distal sites.  All monkeys at 6 and 10 dpi were systemically infected. SIV vRNA+ cells in rectum and LNs were primarily CD4+ T cells revealed using combined ISH/IHC. Host transcriptome analyses revealed a dramatic alteration in host gene expression in the rectum and draining LNs.   Our results indicate that SIV rectal transmission follows a stage dissemination mode and virus infected-cells are primarily CD4+ T cells.  The implications of this study for developing of vaccine and other preventive measures against HIV rectal transmission will be discussed.