Exploring HIV latency using transcription profiling

Abstract

The major barrier to a cure for HIV is the existence of reservoirs consisting predominantly of latently infected CD4+ T cells, which do not produce virus constitutively but can be induced to produce infectious virus on activation. HIV latency research has largely focused on peripheral blood, yet most HIV-infected cells reside in tissues, especially the gut, where differences in drug penetration, cell types, and immune responses may impact mechanisms of persistence. Exploring the differences between the gut and the blood in transcriptional blocks may reveal fundamental insights into mechanisms that contribute to HIV latency. Our novel transcriptional profiling assays enable us to determine where blocks to HIV transcription occur in various tissues and the magnitude of their contribution. These assays could also be adapted to investigate latency established by other retroviridae or even DNA viruses such as herpesviridae with a view to pinpointing mechanisms underlying latency in vivo and ultimately contribute to designing a cure.