Abstract |
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.
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Authors | Mark K Lafferty, Lingling Sun, Leon DeMasi, Wuyuan Lu, Alfredo Garzino-Demo |
Journal | Blood
(Blood)
Vol. 115
Issue 8
Pg. 1564-71
(Feb 25 2010)
ISSN: 1528-0020 [Electronic] United States |
PMID | 20023216
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Apolipoproteins B
- CCR6 protein, human
- Receptors, CCR5
- Receptors, CCR6
- Pertussis Toxin
- APOBEC-3G Deaminase
- APOBEC3G protein, human
- Cytidine Deaminase
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Topics |
- APOBEC-3G Deaminase
- Apolipoproteins B
(biosynthesis, immunology)
- Cytidine Deaminase
(immunology)
- Enzyme Induction
(drug effects, immunology)
- HIV
(immunology, metabolism)
- HIV Infections
(immunology, transmission)
- Humans
- Pertussis Toxin
(pharmacology)
- Receptors, CCR5
(immunology, metabolism)
- Receptors, CCR6
(immunology, metabolism)
- T-Lymphocytes, Helper-Inducer
(immunology, metabolism)
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