Detection of HIV-1 mRNA in latently infected CD4+ T cells

Latent HIV-1 provirus in infected individuals on suppressive therapy does not always remain transcriptionally silent. Both HIV-1 LTR and human gene promoter derived transcriptional events can contribute HIV-1 sequences to the mRNA produced in the cell. In addition, mRNA sequences containing both human and viral gene sequences can arise through the processes of readthrough transcription and aberrant splicing. To elucidate the nature of these aberrant transcripts, we used target enrichment-coupled RNA-Seq to detect HIV-1-sequence-containing mRNA in latently infected cells from a primary cell model and ex vivo patient samples. Our study provides clues to the characteristics of HIV-1 integrants and the splicing patterns that promote formation of these aberrant transcripts. This investigation provides insights into the HIV-1 mRNA footprint in latently infected cells and potential post-transcriptional mechanisms for the maintenance of latent HIV-1.