Inhibition of HIV-1 Integration in Ex Vivo -Infected CD4 T Cells from Elite Controllers

Abstract

Elite controllers spontaneously maintain undetectable levels of HIV-1 replication for reasons that remain unclear. Here, we show that in elite controllers, direct ex vivo infection of purified CD4 T cells without prior in vitro activation results in disproportionately low levels of integrated HIV-1 DNA relative to the quantity of reverse transcripts, while the levels of two-long terminal repeat (2-LTR) circles were excessively elevated relative to those of integrated HIV-1 DNA. This indicates that chromosomal HIV-1 integration is inhibited in ex vivo- infected CD4 T cells from elite controllers. This defect in HIV-1 integration was unrelated to p21, a host protein that can restrict early HIV-1 replication steps, and was not visible following infection of in vitro- activated CD4 T cells from elite controllers. These data contribute to increasing evidence that intrinsic inhibition of specific HIV-1 replication steps plays an important role in the ability of elite controllers to maintain undetectable viral loads.