Limited sequence variation and similar phenotypic characteristics of HIV-1 subtype C Gag variants derived from the reservoir and pre-therapy plasma

Latent reservoirs are a barrier to achieving long-term remission of HIV, as the dormant virus can be reactivated if therapy is discontinued. A combination approach of latency reversal agents and a cytotoxic T lymphocyte (CTL)-based therapeutic vaccine or other immunomodulatory agents to eliminate the reactivated viruses, is being explored for virus eradication. Investigation of whether viral variants present in the reservoir differ from those circulating in peripheral blood prior to treatment initiation, could better inform immune-based interventions for HIV cure. Further, most previous reservoir studies focussed on peripheral blood, however it is also relevant to study the reservoir in tissues. Here, we characterised the viral variants in the peripheral blood and lymph node reservoir in comparison to those in pre-therapy plasma. We focussed on the Gag protein as it is a major target of CTL-based therapeutic vaccines and influences replication ability of the virus as well as susceptibility to antiviral cytokines. Results showed limited novel mutations and a similar extent of CTL escape in the reservoir variants compared to the pre-therapy variants. The novel Gag mutations in the reservoir variants did not significantly alter virus characteristics overall, and are therefore unlikely to affect effectiveness of immune-based interventions for virus eradication.