Arsenic modulates APOBEC3G-mediated restriction to HIV-1 infection in myeloid dendritic cells.
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.
Stalder
Romaine
R
Departments of Dermatology and Venereology and Microbiology and Molecular Medicine, University Hospital and Medical School of Geneva, Switzerland.
Blanchet
Fabien
F
Mangeat
Bastien
B
Piguet
Vincent
V
D000071480:APOBEC-3G Deaminase; D020087:Alu Elements; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D003564:Cytidine Deaminase / Q000502:physiology*; D003713:Dendritic Cells / Q000821:virology*; D057809:HEK293 Cells; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D022423:Myeloid Cells / Q000821:virology*; D010087:Oxides / Q000494:pharmacology*; D018626:Retroelements; D056189:Viral Tropism
D000970:Antineoplastic Agents; D001152:Arsenicals; D016898:Interferon-alpha; D010087:Oxides; D018626:Retroelements; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase; D000077237:Arsenic Trioxide