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* AIDS Pathogenesis and Clinical Research Program, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia;
Department of Medicine, Monash University, Melbourne, Victoria, Australia;
Gladstone Institute of Virology and Immunology, San Francisco, CA 94158;
Infectious Diseases Unit, Alfred Hospital, Melbourne, Victoria, Australia;
¶ Virology Program, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia; and
|| Department of Microbiology, Monash University, Melbourne, Victoria, Australia
HIV-1 persists in peripheral blood monocytes in individuals receiving highly active antiretroviral therapy (HAART) with viral suppression, despite these cells being poorly susceptible to infection in vitro. Because very few monocytes harbor HIV-1 in vivo, we considered whether a subset of monocytes might be more permissive to infection. We show that a minor CD16+ monocyte subset preferentially harbors HIV-1 in infected individuals on HAART when compared with the majority of monocytes (CD14highCD16–). We confirmed this by in vitro experiments showing that CD16+ monocytes were more susceptible to CCR5-using strains of HIV-1, a finding that is associated with higher CCR5 expression on these cells. CD16+ monocytes were also more permissive to infection with a vesicular stomatitis virus G protein-pseudotyped reporter strain of HIV-1 than the majority of monocytes, suggesting that they are better able to support HIV-1 replication after entry. Consistent with this observation, high molecular mass complexes of apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G (APOBEC3G) were observed in CD16+ monocytes that were similar to those observed in highly permissive T cells. In contrast, CD14highCD16– monocytes contained low molecular mass active APOBEC3G, suggesting this is a mechanism of resistance to HIV-1 infection in these cells. Collectively, these data show that CD16+ monocytes are preferentially susceptible to HIV-1 entry, more permissive for replication, and constitute a continuing source of viral persistence during HAART.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Health and Medical Research Council Program Grant and American Foundation for AIDS Research Grant 106368-33-RGRL.
2 P.J.E. and E.T. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Suzanne M Crowe, Macfarlane Burnet Institute for Medical Research and Public Health, 85 Commercial Road, Melbourne, Victoria, Australia 3004. E-mail address: crowe{at}burnet.edu.au
4 Abbreviations used in this paper: HAART, highly active antiretroviral therapy; APOBEC3G, apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G; HMM, high molecular mass; LMM, low molecular mass; LTR, long terminal repeat; RTU, reverse transcriptase unit; VSV-G, vesicular stomatitis virus envelope glycoprotein.
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