title: Alpha interferon potently enhances the anti-human immunodeficiency virus type 1 activity of APOBEC3G in resting primary CD4 T cells.
abstract: The interferon (IFN) system, including various IFNs and IFN-inducible gene products, is well known for its potent innate immunity against wide-range viruses. Recently, a family of cytidine deaminases, functioning as another innate immunity against retroviral infection, has been identified. However, its regulation remains largely unknown. In this report, we demonstrate that through a regular IFN-alpha/beta signal transduction pathway, IFN-alpha can significantly enhance the expression of apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) in human primary resting but not activated CD4 T cells and the amounts of APOBEC3G associated with a low molecular mass. Interestingly, short-time treatments of newly infected resting CD4 T cells with IFN-alpha will significantly inactivate human immunodeficiency virus type 1 (HIV-1) at its early stage. This inhibition can be counteracted by APOBEC3G-specific short interfering RNA, indicating that IFN-alpha-induced APOBEC3G plays a key role in mediating this anti-HIV-1 process. Our data suggest that APOBEC3G is also a member of the IFN system, at least in resting CD4 T cells. Given that the IFN-alpha/APOBEC3G pathway has potent anti-HIV-1 capability in resting CD4 T cells, augmentation of this innate immunity barrier could prevent residual HIV-1 replication in its native reservoir in the post-highly active antiretroviral therapy era.
authors.affiliation: Center for Human Virology, Division of Infectious Diseases, Department of Medicine, Thomas Jefferson University, 1040 Locust Street, Philadelphia, PA 19107, USA.
authors.forename: Keyang
authors.initials: K
authors.lastname: Chen
authors.forename: Jialing
authors.initials: J
authors.lastname: Huang
authors.forename: Chune
authors.initials: C
authors.lastname: Zhang
authors.forename: Sophia
authors.initials: S
authors.lastname: Huang
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nunnari
authors.forename: Feng-xiang
authors.initials: FX
authors.lastname: Wang
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Tong
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.forename: Kristi
authors.initials: K
authors.lastname: Nikisher
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
mesh_terms: D016475:3T3 Cells; D000071480:APOBEC-3G Deaminase; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D003564:Cytidine Deaminase; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D009700:Nucleoside Deaminases / Q000378:metabolism*; D017393:RNA Editing; D034741:RNA, Small Interfering / Q000494:pharmacology; D012097:Repressor Proteins / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase