The HIV-2 proviral landscape is dominated by defective proviruses

Abstract

Background: Compared with HIV-1 infection, HIV-2 infection is associated with a slower progression to AIDS. Understanding the persistence of HIV-2 infection might inform the mechanisms responsible for differences in the pathogenicity of HIV-2 versus HIV-1. Methods: In this study, we analyzed the genetic composition of the proviral reservoir in archived blood samples collected from 13 untreated HIV-2-infected adults from Senegal. We used single-genome, near-full-length individual proviral sequencing (FLIP-Seq) to assess the relative frequency of intact and defective proviruses. Results: Ten out of 13 (77%) study subjects demonstrated virologic suppression (<90 HIV RNA copies/ml) while the remaining 3 (23%) had detectable HIV RNA. We obtained 363 proviral sequences from peripheral blood mononuclear cells (PBMCs) from the 13 study subjects. Within these sequences, 342 (94%) defective proviruses were detected. Twenty-one (6%) intact proviruses were detected from three study subjects, with one study subject displaying a large clone consisting of 16 genome-intact sequences. Conclusion: This data suggests that similar to HIV-1 infection, the proviral landscape of HIV-2 is dominated by defective proviruses.

Targeting Viral Transcription for HIV Cure Strategies

“…Most HIV studies are focused on the HIV-1 variant; however, HIV-2 should not be neglected as an estimated 2 million people worldwide are living with this infection, and there might be differences in the mechanisms that regulate HIV-2 persistence and latency. Recently, Koofhethile et al observed that the HIV-2 proviral landscape is dominated by defective proviruses, similar to what happens in HIV-1 infection [142]. Nonetheless, although HIV-2 LTR is similar to HIV-1 LTR, it contains a duplicated TAR RNA stem-loop structure [143] and is less responsive to CD4+ T cell activation signals [144].…”