title: The CD16+ monocyte subset is more permissive to infection and preferentially harbors HIV-1 in vivo.
abstract: 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.
authors.affiliation: AIDS Pathogenesis and Clinical Research Program, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Ellery
authors.forename: Emma
authors.initials: E
authors.lastname: Tippett
authors.forename: Ya-Lin
authors.initials: YL
authors.lastname: Chiu
authors.forename: Geza
authors.initials: G
authors.lastname: Paukovics
authors.forename: Paul U
authors.initials: PU
authors.lastname: Cameron
authors.forename: Ajantha
authors.initials: A
authors.lastname: Solomon
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewin
authors.forename: Paul R
authors.initials: PR
authors.lastname: Gorry
authors.forename: Anthony
authors.initials: A
authors.lastname: Jaworowski
authors.forename: Warner C
authors.initials: WC
authors.lastname: Greene
authors.forename: Secondo
authors.initials: S
authors.lastname: Sonza
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Crowe
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D004198:Disease Susceptibility / Q000276:immunology / Q000473:pathology / Q000821:virology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007424:Intracellular Fluid / Q000276:immunology* / Q000821:virology*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D009000:Monocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D015728:Receptors, HIV / Q000096:biosynthesis / Q000235:genetics; D017452:Receptors, IgG / Q000096:biosynthesis* / Q000097:blood; D014779:Virus Replication / Q000276:immunology
chemical_list: D018950:Lipopolysaccharide Receptors; D015728:Receptors, HIV; D017452:Receptors, IgG