title: Involvement of NF-κB in changes of IFN-γ-induced CIITA/MHC-II and iNOS expression by influenza virus in macrophages.
abstract: Type II interferon (IFN-γ) plays an important role in defense against viral infection. Although this cytokine is found during influenza virus infection, it seems to have no protective function against the virus, and the reasons for this are not clear. To determine how the influenza virus overcomes the antiviral effects of IFN-γ, we examined the effect of A/Puerto-Rico/8/34 (H1N1) (PR8) infection on the expression of various IFN-γ inducible genes involved in defense against virus infection. The results showed that PR8 selectively affects IFN-γ induced MHC-II and iNOS expression in both the murine macrophage-like cell line, Raw264.7, and in primary alveolar macrophages. Infection of IFN-γ treated macrophages with PR8 resulted in decreased expression of CIITA/MHC-II and increased production of iNOS/NO. These changes correlate with activation of NF-κB but not with JAK/STAT signaling. The data indicate one possible mechanism underlying the ineffectiveness of IFN-γ against influenza virus, and suggest that NF-κB may be a promising target for anti-influenza drugs.
authors.affiliation: Virology Division, National Veterinary Research and Quarantine Service, Ministry for Food, Agriculture, Forestry and Fisheries, Anyang, Gyeonggido, Republic of Korea.
authors.forename: Do Thi Thu
authors.initials: do TT
authors.lastname: Hang
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Song
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Jin-Woo
authors.initials: JW
authors.lastname: Park
authors.forename: Yeun-Kyung
authors.initials: YK
authors.lastname: Shin
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology*; D053612:Janus Kinases / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology* / Q000821:virology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D009975:Orthomyxoviridae / Q000187:drug effects / Q000502:physiology*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000821:virology; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D016328:NF-kappa B; D009687:Nuclear Proteins; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D009569:Nitric Oxide; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D053612:Janus Kinases