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Lymphocytes recruited by chemokine CXCL9 are known to be important in control of HSV-2 infection in mice, although the underlying mechanism remains to be addressed. Based on our observation that CXCL9 expression is augmented in the cervical mucus of HSV-2\u2013positive women, in this study we demonstrate that HSV-2 infection directly induces CXCL9 expression in primary cervical epithelial cells and cell lines, the principal targets of HSV-2, at both mRNA and protein levels. Further studies reveal that the induction of CXCL9 expression by HSV-2 is dependent upon a binding site for C\/EBP-\u03b2 within CXCL9 promoter sequence. Furthermore, CXCL9 expression is promoted at the transcriptional level through phosphorylating C\/EBP-\u03b2 via p38 MAPK pathway, leading to binding of C\/EBP-\u03b2 to the CXCL9 promoter. Chemotaxis assays indicate that upregulation of CXCL9 expression at the protein level by HSV-2 infection enhances the migration of PBLs and CD4+ T cells, whereas neutralization of CXCL9 or inhibition of p38-C\/EBP-\u03b2 pathway can significantly decrease the migration. Our data together demonstrate that HSV-2 induces CXCL9 expression in human cervical epithelial cells by activation of p38-C\/EBP-\u03b2 pathway through promoting the binding of C\/EBP-\u03b2 to CXCL9 promoter, which may recruit activated CD4+ T cells to mucosal HSV-2 infection sites and potentially increase the risk of HIV-1 sexual transmission.<\/jats:p>","DOI":"10.4049\/jimmunol.1103706","type":"journal-article","created":{"date-parts":[[2012,5,15]],"date-time":"2012-05-15T01:56:02Z","timestamp":1337046962000},"page":"6247-6257","source":"Crossref","is-referenced-by-count":51,"title":["Herpes Simplex Virus Type 2 Infection of Human Epithelial Cells Induces CXCL9 Expression and CD4+ T Cell Migration via Activation of p38-CCAAT\/Enhancer-Binding Protein-\u03b2 Pathway"],"prefix":"10.1093","volume":"188","author":[{"given":"Wenjie","family":"Huang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071 ,","place":["China"]},{"name":"Graduate School, Chinese Academy of Sciences , Beijing 100049 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukun","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071 ,","place":["China"]},{"name":"Graduate School, Chinese Academy of Sciences , Beijing 100049 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mudan","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071 ,","place":["China"]},{"name":"Graduate School, Chinese Academy of Sciences , Beijing 100049 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071 ,","place":["China"]},{"name":"Graduate School, Chinese Academy of Sciences , Beijing 100049 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Jin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071 ,","place":["China"]},{"name":"Graduate School, Chinese Academy of Sciences , Beijing 100049 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalan","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George E","family":"Griffin","sequence":"additional","affiliation":[{"name":"Center for Infection and Immunity, St. George\u2019s University of London , London SW17 0RE ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin J","family":"Shattock","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, Faculty of Medicine, Imperial College London, St. Mary\u2019s Campus , London W2 1PG ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinxue","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071 ,","place":["China"]},{"name":"Center for Infection and Immunity, St. George\u2019s University of London , London SW17 0RE ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,6,15]]},"reference":[{"key":"2025032410161353700_r1","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/S1473-3099(08)70181-6","article-title":"Herpes simplex virus and HIV-1: deciphering viral synergy","volume":"8","author":"Van de Perre","year":"2008","journal-title":"Lancet Infect. 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