Arsenic modulates APOBEC3G-mediated restriction to HIV-1 infection in myeloid dendritic cells

• Published in: Journal of leukocyte biology Vol. 88; no. 6; pp. 1251 - 1258
• Main Authors: Stalder, Romaine, Blanchet, Fabien, Mangeat, Bastien, Piguet, Vincent
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.12.2010
• Subjects: Adaptive immunology; Alu Elements; Antineoplastic Agents - pharmacology; APOBEC-3G Deaminase; Arsenicals - pharmacology; Cellular Biology; Cytidine Deaminase - physiology; Dendritic Cells - virology; HEK293 Cells; HIV-1 - drug effects; Human immunodeficiency virus 1; Humans; Immunology; Innate immunity; Interferon-alpha - pharmacology; Life Sciences; Microbiology and Parasitology; Myeloid Cells - virology; Oxides - pharmacology; primary cells; Retroelements; retrovirus; subcellular localization; Viral Tropism; Virology
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.0310176

An APOBEC3G‐dependent restriction operates in blood‐derived myeloid dendritic cells, which can be relieved by arsenic trioxide. DC are major targets of HIV‐1 during the early events of infection. Yet, HIV‐1 infects these cells only inefficiently in vitro as compared with CD4+T lymphocytes. Accordingly, we have previously identified a strong post‐entry block to HIV‐1 replication in MDDC as a result of the cellular restriction factor A3G. Furthermore, we have demonstrated that As2O3, a drug used to treat acute promyelocytic leukemia, can fully eliminate the potent post‐entry restriction of HIV‐1 infection in MDDC and in blood‐derived MyDC by mechanisms that were unclear. We are now exploring the interplay between As2O3 and A3G‐mediated restriction in primary DC subsets. Here, we report that As2O3 counteracts A3G‐mediated restriction in MyDC but not in MDDC. RNAi of A3G in MyDC indicated that the As2O3‐mediated increase of HIV‐1 infection was largely dependent on the presence of the cellular restriction factor. This study reveals an unexpected interplay between As2O3 and A3G‐mediated restriction to HIV‐1 infection in primary human MyDC.