The latent HIV-1 reservoir primarily resides in resting CD4؉ T cells which are a heterogeneous population composed of both naive (T N ) and memory cells. In HIV-1-infected individuals, viral DNA has been detected in both naive and memory CD4 ؉ T cell subsets although the frequency of HIV-1 DNA is typically higher in memory cells, particularly in the central memory (T CM ) cell subset. T N and T CM cells are distinct cell populations distinguished by many phenotypic and physiological differences. In this study, we used a primary cell model of HIV-1 latency that utilizes direct infection of highly purified T N and T CM cells to address differences in the establishment and reversal of HIV-1 latency. Consistent with what is seen in vivo, we found that HIV-1 infected T N cells less efficiently than T CM cells. However, when the infected T N cells were treated with latency-reversing agents, including anti-CD3/CD28 antibodies, phorbol myristate acetate/phytohemagglutinin, and prostratin, as much (if not more) extracellular virion-associated HIV-1 RNA was produced per infected T N cell as per infected T CM cell. There were no major differences in the genomic distribution of HIV-1 integration sites between T N and T CM cells that accounted for these observed differences.
We observed decay of the latent HIV-1 cells in both T cell subsets after exposure to each of the latency-reversing agents. Collectively, these data highlight significant differences in the establishment and reversal of HIV-1 latency in T N and T CM CD4؉ T cells and suggest that each subset should be independently studied in preclinical and clinical studies.
IMPORTANCE
The latent HIV-1 reservoir is frequently described as residing within resting memory CD4؉ T cells. This is largely due to the consistent finding that memory CD4 ؉ T cells, specifically the central (T CM )