title: Regulation of interferon-alpha-inducible cellular genes in human immunodeficiency virus-infected monocytes.
abstract: Cellular mechanisms that control susceptibility to opportunistic infection in human immunodeficiency virus (HIV)-infected individuals remain poorly understood. HIV may induce certain cellular genes that restrict HIV replication and protect cells against other superinfecting viral pathogens. Indeed, HIV-infected monocytes resist infection by vesicular stomatitis virus (VSV). HIV-induced VSV interference in monocytes increases with time after HIV infection. Such interference was evident 6 h after HIV infection and reached maximal levels at 14 days. Monocytotropic but not T cell-tropic HIV strains elicited these effects, signaling a requirement for viral entry and/or replication. Viral interference was independent of interferon (IFN) and was unaffected by addition of neutralizing IFN-alpha and -beta antibodies. The well-described IFN-alpha-inducible antiviral pathways were examined to determine their relationship to the cellular mechanism(s) underlying VSV interference. HIV and IFN-alpha both induced the expression of 2-5A synthetase and Mx gene. In contrast, the guanylate-binding protein (GBP), 6-16, and 9-27 cellular genes were up-regulated by IFN-alpha but not HIV. MxA was detected in HIV-infected monocytes but not in uninfected monocytes. The association between Mx expression and resistance to VSV, coupled with previously described anti-VSV activities by human MxA, suggested that Mx may be an effector molecule for the HIV-induced anti-VSV activities. These results, taken together, suggest that HIV can induce antiviral cellular gene expression, independent of IFN.
authors.affiliation: Department of Medicine, University of Nebraska Medical Center, Omaha 68194.
authors.forename: L M
authors.initials: LM
authors.lastname: Baca
authors.forename: P
authors.initials: P
authors.lastname: Genis
authors.forename: D
authors.initials: D
authors.lastname: Kalvakolanu
authors.forename: G
authors.initials: G
authors.lastname: Sen
authors.forename: M S
authors.initials: MS
authors.lastname: Meltzer
authors.forename: A
authors.initials: A
authors.lastname: Zhou
authors.forename: R
authors.initials: R
authors.lastname: Silverman
authors.forename: H E
authors.initials: HE
authors.lastname: Gendelman
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000032:analysis; D000998:Antiviral Agents / Q000032:analysis / Q000235:genetics / Q000502:physiology; D001483:Base Sequence; D015152:Blotting, Northern; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000032:analysis / Q000235:genetics; D005455:Fluorescent Antibody Technique; D019204:GTP-Binding Proteins; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006678:HIV / Q000302:isolation & purification* / Q000502:physiology; D015658:HIV Infections / Q000503:physiopathology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007372:Interferons / Q000378:metabolism / Q000502:physiology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology* / Q000201:enzymology / Q000382:microbiology*; D064547:Myxovirus Resistance Proteins; D016133:Polymerase Chain Reaction / Q000379:methods; D011506:Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology; D012194:RNA-Directed DNA Polymerase; D015854:Up-Regulation; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D004247:DNA; D007372:Interferons; D003513:Cycloheximide; D012194:RNA-Directed DNA Polymerase; D015088:2',5'-Oligoadenylate Synthetase; D019204:GTP-Binding Proteins