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

Infectious Disease Division, Massachusetts General Hospital, Boston, MA 02114. .
Journal of Virology (Impact Factor: 4.65). 09/2011; 85(18):9646-50. DOI: 10.1128/JVI.05327-11
Source: PubMed

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.

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Available from: Xu G. Yu, Jan 15, 2014
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