CCR6 ligands inhibit HIV by inducing APOBEC3G.
We have identified a post-entry CCR6-dependent mechanism of inhibition of HIV occurring at an early stage of infection mediated by the induction of the host restriction factor apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G). We observed induction of APOBEC3G expression only in CCR6(+) cells but not in cells treated with the G inhibitory (Gi) pathway inhibitor pertussis toxin. CCR6 is highly expressed on peripheral blood CD4(+)CCR5(+) memory T cells and by 2 populations of CD4(+) T cells within the gut, alpha4beta7(+) and T helper type 17, that have been implicated in cell-to-cell spread of HIV and enhanced restoration of CD4(+) T cells within gut-associated lymphoid tissue, respectively. This novel CCR6-mediated mechanism of inhibition allows the identification of pathways that induce intrinsic immunity to HIV, which could be useful in devising novel therapeutics that selectively target CCR6(+) cells.
Lafferty
Mark K
MK
Division of Basic Science, Institute of Human Virology, Department of Microbiology and Immunology, University of Maryland School of Medicine, 725 Lombard Street, Baltimore, MD 21201, USA.
Sun
Lingling
L
DeMasi
Leon
L
Lu
Wuyuan
W
Garzino-Demo
Alfredo
A
D000071480:APOBEC-3G Deaminase; D001055:Apolipoproteins B / Q000096:biosynthesis / Q000276:immunology; D003564:Cytidine Deaminase / Q000276:immunology*; D004790:Enzyme Induction / Q000187:drug effects / Q000276:immunology; D006678:HIV / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission; D006801:Humans; D037342:Pertussis Toxin / Q000494:pharmacology; D019713:Receptors, CCR5 / Q000276:immunology / Q000378:metabolism; D054399:Receptors, CCR6 / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism
D001055:Apolipoproteins B; C106311:CCR6 protein, human; D019713:Receptors, CCR5; D054399:Receptors, CCR6; D037342:Pertussis Toxin; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase