HIV latency is influenced by regions of the viral genome outside of the long terminal repeats and regulatory genes.

We have previously described an in vitro primary thymocyte model for HIV latency that recapitulates several important aspects of latently infected cells obtained from patients. Our original model included a truncated HIV genome expressing only Tat, Rev, and Vpu along with a reporter gene. We have now expanded these studies to include reporter viruses encoding more complete viral genomes. We show here that regions of the viral genome outside of the long terminal repeat promoter and Tat/Rev regulatory genes can substantially affect both the basal level of HIV transcription prior to stimulation, and also the level of viral expression following costimulation via CD3 and CD28 ligation. These differences in latency phenotype between truncated and more complete HIV genomes demonstrate the importance of accessory genes in the context of HIV latency and indicate that care should be taken when interpreting data derived from heavily modified HIV genomes in latency models.