title: 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.
authors: Infectious Disease Division, Massachusetts General Hospital, Boston, MA 02114. mlichterfeld@partners.org.
authors: Maria J
authors: MJ
authors: Buzon
authors: Katherine
authors: K
authors: Seiss
authors: Robert
authors: R
authors: Weiss
authors: Abraham L
authors: AL
authors: Brass
authors: Eric S
authors: ES
authors: Rosenberg
authors: Florencia
authors: F
authors: Pereyra
authors: Xu G
authors: XG
authors: Yu
authors: Mathias
authors: M
authors: Lichterfeld
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002478:Cells, Cultured; D015658:HIV Infections / Q000276:immunology*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D016662:Virus Integration