title: Cell-specific regulation of APOBEC3F by interferons.
abstract: Human cytidine deaminase APOBEC3F (A3F) has broad anti-viral activity against hepatitis B virus and retroviruses including human immunodeficiency virus type 1. However, its regulation in viral natural target cells such CD4+ T lymphocytes, macrophages, and primary liver cells has not been well studied. Here we showed that A3F was up-regulated by interferon (IFN)-alpha in primary hepatocytes and multiple liver cell lines as well as macrophages. Although the IFN-alpha signaling pathway was active in T lymphoid cells and induction of other IFN stimulated genes such as PKR was detected, A3F and APOBEC3G (A3G) were not induced by IFN-alpha in these cells. Thus, additional factors other than known IFN-stimulated genes also regulated IFN-alpha-induced A3F expression distinctly. A3F and A3G expression levels in primary hepatocytes, especially after IFN-alpha stimulation, were comparable to those in CD4+ T lymphocytes in some individuals. Significant variations of A3F and A3G expression in primary hepatocytes from various subjects were observed. Individual variations in A3F and/or A3G regulation and expression might influence the clinical outcomes of hepatitis B infection.
authors.affiliation: Second Affiliated Hospital, Cancer Institute, School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Songcheng
authors.initials: S
authors.lastname: Ying
authors.forename: Xuzhao
authors.initials: X
authors.lastname: Zhang
authors.forename: Phuong Thi Nguyen
authors.initials: PT
authors.lastname: Sarkis
authors.forename: Rongzhen
authors.initials: R
authors.lastname: Xu
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Yu
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D043525:Cytosine Deaminase / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D017393:RNA Editing / Q000187:drug effects / Q000235:genetics; D012190:Retroviridae / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; C492906:APOBEC3F protein, human; D043525:Cytosine Deaminase