Elimination of Human Immunodeficiency Virus Reservoirs Harboring Intact Proviruses.

Abstract

Human immunodeficiency virus (HIV) establishes persistent infection by integrating its proviral DNA into the host genome. While most integrated proviruses are defective, a small portion of proviruses are intact that represent a major obstacle to achieving an HIV cure. We have designed an approach for selective elimination of host cells harboring replication-competent HIV (SECH), through inhibition of autophagy and anti-apoptotic molecules during viral reactivation. However, the effects of SECH on the dynamics of intact and defective HIV provirus remain unclear. We isolated DNA from HIV-infected samples after SECH treatments. We analyzed HIV type 1 (HIV-1) proviruses in these samples by intact proviral DNA assay, near full-length polymerase chain reaction (PCR), and DNA sequencing analyses. We show that SECH treatments reduce reservoirs harboring intact but not defective HIV proviruses by intact proviral DNA assay. Nested PCR and DNA sequencing analyses confirm that SECH treatments can delete full-length HIV-1 proviruses in humanized mice in vivo and in patient samples ex vivo. Our data suggest that the SECH method is capable of effectively targeting HIV reservoirs harboring intact HIV proviruses that can restart active viral replication.