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J Virol. 2011 Sep;85(18):9646-50. doi: 10.1128/JVI.05327-11. Epub 2011 Jul 6.

Inhibition of HIV-1 integration in ex vivo-infected CD4 T cells from elite controllers.

Author information

  • 1Infectious Disease Division, Massachusetts General Hospital, Boston, MA 02114. mlichterfeld@partners.org.

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.

PMID:
21734042
[PubMed - indexed for MEDLINE]
PMCID:
PMC3165766
Free PMC Article

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