APOBEC3G upregulation by alpha interferon restricts human immunodeficiency virus type 1 infection in human peripheral plasmacytoid dendritic cells

• Published in: Journal of general virology 2008-03, Vol.89 (3), p.722-730
• Main Authors: Wang, Feng-xiang, Huang, Jialing, Zhang, Hangxiang, Ma, Xinliang, Zhang, Hui
• Format: Article
• Language: English
• Subjects: Antiviral Agents - immunology; Antiviral Agents - metabolism; Antiviral Agents - pharmacology; APOBEC-3G Deaminase; Biological and medical sciences; Cells, Cultured; Cytidine Deaminase - metabolism; Dendritic Cells - metabolism; Dendritic Cells - virology; Fundamental and applied biological sciences. Psychology; HIV Infections - immunology; HIV Infections - virology; HIV Reverse Transcriptase - antagonists & inhibitors; HIV-1 - drug effects; HIV-1 - enzymology; Human immunodeficiency virus 1; Humans; Interferon-alpha - immunology; Interferon-alpha - metabolism; Interferon-alpha - pharmacology; Microbiology; Miscellaneous; Up-Regulation; Virology
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.83530-0

1 Center for Human Virology, Division of Infectious Diseases, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA 2 Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA Correspondence Hui Zhang hui.zhang{at}jefferson.edu 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- ) 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- production in reaction to various stimuli. In this report, we demonstrate that IFN- , 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- 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- -induced A3G plays a key role in mediating pDCs response to HIV-1. Given the central role played by pDCs in orchestrating the IFN- /A3G intercellular network and intracellular signal pathway, our data indicate that pDCs themselves are also protected by an IFN- /A3G-mediated innate immunity barrier from HIV-1 infection.