{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T05:18:26Z","timestamp":1789190306975,"version":"build-2803163510"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,4,16]]},"abstract":"<jats:p>Interferons constitute the earliest immune response against viral infection. They elicit antiviral effects as well as multiple biological responses involved in cell growth regulation and immune activation. Because the interferon-induced cellular antiviral response is the primary defense mechanism against viral infection, many viruses have evolved strategies to antagonize the inhibitory effects of interferon. Here, we demonstrate a strategy that Kaposi's sarcoma-associated herpesvirus uses to block virus-mediated induction of type I interferon. We found that a viral immediate-early protein, namely ORF45, interacts with cellular interferon-regulatory factor 7 (IRF-7). In consequence, IRF-7 phosphorylation is inhibited and the accumulation of IRF-7 in the nucleus in response to viral infection is blocked. IRF-7 is a transcription regulator that is responsible for virus-mediated activation of type I interferon genes. By blocking the phosphorylation and nuclear translocation of IRF-7, ORF45 efficiently inhibits the activation of interferon \u03b1 and \u03b2 genes during viral infection. Inhibition of interferon gene expression through a viral protein blocking the activation and nuclear translocation of a crucial transcription factor is a novel mechanism for viral immune evasion.<\/jats:p>","DOI":"10.1073\/pnas.082420599","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:45:09Z","timestamp":1027680309000},"page":"5573-5578","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":212,"title":["A Kaposi's sarcoma-associated herpesviral protein inhibits virus-mediated induction of type I interferon by blocking IRF-7 phosphorylation and nuclear accumulation"],"prefix":"10.1073","volume":"99","author":[{"given":"Fan Xiu","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania School of Dental Medicine, Philadelphia, PA 19104; and Department of Pathology, New York University School of Medicine, New York, NY 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10016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania School of Dental Medicine, Philadelphia, PA 19104; and Department of Pathology, New York University School of Medicine, New York, NY 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2002,4,9]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.67.1.227"},{"key":"e_1_3_3_2_2","first-page":"375","volume-title":"Fields Virology","author":"Vilcek J","year":"1996","unstructured":"J Vilcek, G Sen Fields Virology, eds B N Fields, D M Knipe, P M Howley (Lippincott-Raven, Philadelphia), pp. 375\u2013399 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