Intrarectal challenge restricts SIVmac239M viral lineages compared to intravenous challenge.

Little is known about how specific individual virus lineages that replicate systemically during acute HIV/SIV infection persist into chronic infection. In this study, we use SIVmac239M, a modified version of the pathogenic research strain SIVmac239, to track SIV lineages up to 12 weeks after intravenous and intrarectal infection. This modified virus strain contains a 34 nucleotide molecular barcode inserted between the Vpx and Vpr genes, with the entire stock containing approximately 10,000 unique versions of this barcode. Two Mafa-A1*063+ cynomolgus macaques (Macaca fascicularis) were challenged intravenously (IV), and two Mamu-A1*001+ rhesus macaques (Macaca mulatta) were challenged intrarectally (IR) with 200,000 Infection Units (IU) of SIVmac239M. We deep sequenced the molecular barcode in replicating SIVmac239M from all animals over the 12 weeks of the study to characterize the diversity and persistence of virus lineages. We also characterized the sequences of the T cell epitopes targeted during acute SIV infection. During the first three weeks post-infection, we found ~150 times more unique virus lineages circulating in the animals challenged intravenously when compared to those challenged intrarectally, which is consistent with the hypothesis that the challenge route is the primary driver restricting the transmission of individual viral lineages. We also find that the emergence of T cell escape variants in acutely targeted epitopes can occur on multiple virus templates, but that elimination of some of these templates is likely a consequence of additional host factors. Even though this is a small data set, it implies that virus lineages present during acute infection can still be eliminated from the systemic virus population during chronic infection.