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Flavivirus infections quickly activate nuclear factor kappa B (NF-\u03baB), and salicylates have been shown to inhibit NF-\u03baB activation. In this study, we investigated whether salicylates suppress flavivirus replication and virus-induced apoptosis in cultured cells. In a dose-dependent inhibition, we found salicylates within a range of 1 to 5 mM not only restricted flavivirus replication but also abrogated flavivirus-triggered apoptosis. However, flavivirus replication was not affected by a specific NF-\u03baB peptide inhibitor, SN50, and a proteosome inhibitor, lactacystin. Flaviviruses also replicated and triggered apoptosis in cells stably expressing I\u03baB\u03b1-\u0394N, a dominant-negative mutant that antagonizes NF-\u03baB activation, as readily as in wild-type BHK-21 cells, suggesting that NF-\u03baB activation is not essential for either flavivirus replication or flavivirus-induced apoptosis. Salicylates still diminished flavivirus replication and blocked apoptosis in the same I\u03baB\u03b1-\u0394N cells. This inhibition of flaviviruses by salicylates could be partially reversed by a specific p38 mitogen-activated protein (MAP) kinase inhibitor, SB203580. Together, these results show that the mechanism by which salicylates suppress flavivirus infection may involve p38 MAP kinase activity but is independent of blocking the NF-\u03baB pathway.<\/jats:p>","DOI":"10.1128\/jvi.75.17.7828-7839.2001","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:06:37Z","timestamp":1027764397000},"page":"7828-7839","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":45,"title":["Salicylates Inhibit Flavivirus Replication Independently of Blocking Nuclear Factor Kappa B Activation"],"prefix":"10.1128","volume":"75","author":[{"given":"Ching-Len","family":"Liao","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology and Immunology,1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Ling","family":"Lin","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology and Immunology,1"},{"name":"<!--label omitted: 2-->National Defense Medical Center, Institute of Biomedical Sciences, Academia Sinica,2 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bi-Ching","family":"Wu","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology and Immunology,1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang-Huei","family":"Tsao","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Graduate Institute of Life Science,3"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei-Chuan","family":"Wang","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology and Immunology,1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiu-I","family":"Liu","sequence":"additional","affiliation":[{"name":"<!--label omitted: 4-->Institute of Preventive Medicine,4 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue-Ling","family":"Huang","sequence":"additional","affiliation":[{"name":"<!--label omitted: 4-->Institute of Preventive Medicine,4 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jui-Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology and Immunology,1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-Pey","family":"Wang","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology and Immunology,1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Kuang","family":"Chen","sequence":"additional","affiliation":[{"name":"<!--label omitted: 5-->Department of Immunology, Buddhist Tzu-Chi Medical College,5Taiwan, Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.69.1.258"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"6338","DOI":"10.4049\/jimmunol.161.11.6338","article-title":"Dengue virus infection of human endothelial cells leads to chemokine production, complement activation, and apoptosis","volume":"161","author":"Avirutnan P.","year":"1998","unstructured":"Avirutnan P. 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