title: Expression and regulation of antiviral protein APOBEC3G in human neuronal cells.
abstract: Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G (APOBEC3G) has recently been identified as a potent antiviral protein. Here, we examined the expression and regulation of APOBEC3G in human brain tissues and the cells of central nervous system (CNS). Similar to the immune cells, human brain tissue and the CNS cells expressed APOBEC3G at both mRNA and protein levels. The expression of APOBEC3G could be up-regulated in human neuronal cells (NT2-N) and astrocytes (U87-MG) by interferons (IFN-alpha, beta and gamma), interleukin-1 (IL-1), and tumor necrosis factor. Other cytokines (IL-4, IL-6 and transforming growth factor beta1) and CC-chemokines (CCL3, 4 and 5), however, had little impact on the expression of APOBEC3G. In addition, pseudotyped HIV-1 infection and cytokine/chemokine-enriched supernatants from lipopolysaccharide-stimulated macrophage cultures induced APOBEC3G expression in NT2-N cells. APOBEC3G expressed in the neuronal cells and astrocytes was biologically functional, as the suppression of APOBEC3G expression by the specific siRNA led to increase of pseudotyped HIV-1 replication in these cells. These findings provide direct and compelling evidence that there is intracellular expression and regulation of functional APOBEC3G in the neuronal cells, which may be one of innate defense mechanisms involved in the neuronal protection in the CNS.
authors.affiliation: Division of Allergy & Immunology, Joseph Stokes, Jr. Research Institute at The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Yan-Jian
authors.initials: YJ
authors.lastname: Wang
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: Shi
authors.initials: S
authors.lastname: Liu
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Kolson
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.forename: Li
authors.initials: L
authors.lastname: Ye
authors.forename: Wen-Zhe
authors.initials: WZ
authors.lastname: Ho
mesh_terms: D000071480:APOBEC-3G Deaminase; D001921:Brain / Q000166:cytology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003564:Cytidine Deaminase / Q000235:genetics* / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000737:chemistry; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D013997:Time Factors
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase