Background:  Rhesus macaque models are important for understanding virus pathogenesis and in the search for an AIDS vaccine. Many virus challenge protocols after vaccination use a high dose of SIV_mac to ensure infection of all control animals after a single challenge administered by intravenous or mucosal application. Many virus variants are predicted to infect the animals under these conditions, which is different from the majority of human infections.

Methods:  We performed single genome amplification (SGA) to identify the full env sequence or a fragment encompassing the highly variable V1-V2 env region from SIV_mac251-challenged animals using plasma from the acute and chronic phase, as well as from the original SIV_mac251 challenge stocks.

Results:  The 2 closely related SIV_mac251 stocks sequenced by SGA showed great diversity of env sequences, with most changes within the V1-V2 region. Despite the stock diversity, a narrow selection of env, traceable back to the stock, were detected during the acute phase in 7 of 9 animals infected by a traumatic mucosal application. In contrast, multiple subswarms were found in 4 of the 6 animals in the chronic phase. Many chronic sequences were not represented in the virus stock, indicating that they represent rare variants and that they replicate continuously.

Conclusions:  Multiple species cross the mucosal barrier and infect the host during a high-dose mucosal infection. Interestingly, one or very few of these variants propagate early in the acute phase, but other transmitted variants may emerge to prominence later. This may be the result of viral fitness, competition, founder effects, or innate mechanisms. These surprising findings also suggest that estimation of the number of transmitted virus variants by analysis during the acute phase is inaccurate, and evaluation of both acute and chronic virus is critical to identify the transmitted variants.