APOBEC3G upregulation by alpha interferon restricts human immunodeficiency virus type 1 infection in human peripheral plasmacytoid dendritic cells.
APOBEC3G (A3G), a member of cytidine deaminase family, has potent anti-human immunodeficiency virus type 1 (HIV-1) activity. It has been demonstrated that alpha interferon (IFN-alpha) can significantly enhance the expression of A3G in human primary resting CD4(+) T-cells, macrophages and primary hepatocytes, subsequently decreasing their viral susceptibility. Plasmacytoid dendritic cells (pDCs) are key effectors in innate host immunity, mediating adaptive immune responses and stimulating IFN-alpha production in reaction to various stimuli. In this report, we demonstrate that IFN-alpha, either exogenously added to- or endogenously secreted by pDCs, can enhance the expression of A3G and its family members such as A3A, A3C and A3F. We have also shown that IFN-alpha can inhibit HIV-1 expression in pDCs. This inhibitory effect could be countered by addition of an A3G-specific short interfering RNA, indicating that IFN-alpha-induced A3G plays a key role in mediating pDCs response to HIV-1. Given the central role played by pDCs in orchestrating the IFN-alpha/A3G intercellular network and intracellular signal pathway, our data indicate that pDCs themselves are also protected by an IFN-alpha/A3G-mediated innate immunity barrier from HIV-1 infection.
Wang
Feng-Xiang
FX
Center for Human Virology, Division of Infectious Diseases, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Huang
Jialing
J
Center for Human Virology, Division of Infectious Diseases, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Zhang
Hangxiang
H
Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Ma
Xinliang
X
Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Zhang
Hui
H
Center for Human Virology, Division of Infectious Diseases, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
D000071480:APOBEC-3G Deaminase; D000998:Antiviral Agents / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism / Q000821:virology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D015854:Up-Regulation
D000998:Antiviral Agents; D016898:Interferon-alpha; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase