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 Blood, 1 July 2007, Vol. 110, No. 1, pp. 393-400.
Prepublished online as a Blood First Edition Paper on March 19, 2007; DOI 10.1182/blood-2006-10-051763.

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PHAGOCYTES

Myeloid differentiation and susceptibility to HIV-1 are linked to APOBEC3 expression

Gang Peng1, Teresa Greenwell-Wild1, Salvador Nares1, Wenwen Jin1, Ke Jian Lei1, Zoila G. Rangel2, Peter J. Munson2, and Sharon M. Wahl1

1 Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD; 2 Mathematical and Statistical Computing Laboratory, Division of Computational Bioscience, Center for Information Technology, National Institutes of Health, Bethesda, MD

HIV-1 recognition by, interaction with, and/or infection of CD4+CCR5+ tissue macrophages and dendritic cells (DCs) play important roles in HIV-1 transmission and pathogenesis. By comparison, circulating CD4+CCR5+ monocytes appear relatively resistant to HIV-1, and a fundamental unresolved question involves deciphering restriction factors unique to this precursor population. Not only do monocytes, relative to macrophages, possess higher levels of the innate resistance factor APOBEC3G, but we uncovered APOBEC3A, not previously associated with anti-HIV activity, as being critical in monocyte resistance. Inversely correlated with susceptibility, silencing of APOBEC3A renders monocytes vulnerable to HIV-1. Differences in promiscuity of monocytes, macrophages, and DCs can be defined, at least partly, by disparities in APOBEC expression, with implications for enhancing cellular defenses against HIV-1.


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