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• W2149083544 abstract "Kaposi's sarcoma-associated herpesvirus (KSHV) carries four genes with homology to human interferon regulatory factors (IRFs). One of these IRFs, the viral interferon regulatory factor 3 (vIRF-3), is expressed in latently infected primary effusion lymphoma (PEL) cells and required for their continuous proliferation. Moreover, vIRF-3 is known to be involved in modulation of the type I interferon (IFN) response. We now show that vIRF-3 also interferes with the type II interferon system and antigen presentation to the adaptive immune system. Starting with an analysis of the transcriptome, we show that vIRF-3 inhibits expression of major histocompatibility complex class II (MHC II) molecules: small interfering RNA (siRNA)-mediated knockdown of vIRF-3 in KSHV-infected PEL cell lines resulted in increased MHC II levels; overexpression of vIRF-3 in KSHV-negative B cells leads to downmodulation of MHC II. This regulation could be traced back to inhibition of class II transactivator (CIITA) transcription by vIRF-3. Reporter assays revealed that the gamma interferon (IFN-γ)-sensitive CIITA promoters PIV and PIII were inhibited by vIRF-3. Consistently, IFN-γ levels increased upon vIRF-3 knockdown in PEL cells. IFN-γ regulation by vIRF-3 was confirmed in reporter assays as well as by upregulation of typical IFN-γ target genes upon knockdown of vIRF-3 in PEL cells. In summary, we conclude that vIRF-3 contributes to the viral immunoevasion by downregulation of IFN-γ and CIITA and thus MHC II expression." @default.
• W2149083544 created "2016-06-24" @default.
• W2149083544 creator A5023254017 @default.
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• W2149083544 date "2011-05-01" @default.
• W2149083544 modified "2023-10-10" @default.
• W2149083544 title "Kaposi's Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor 3 Inhibits Gamma Interferon and Major Histocompatibility Complex Class II Expression" @default.
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• W2149083544 doi "https://doi.org/10.1128/jvi.02123-10" @default.
• W2149083544 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3126280" @default.
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• W2149083544 hasPublicationYear "2011" @default.
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