近日,，F(xiàn)aculty of 1000收錄和點(diǎn)評(píng)了中科院武漢病毒研究所胡勤學(xué)學(xué)科組發(fā)表在The Journal of Immunology（2012 Jun 15；188(12)：6247-57）上的HSV-2和HIV-1黏膜共感染論文,，認(rèn)為該研究發(fā)現(xiàn)提出了HSV-2感染增加HIV-1黏膜傳播的潛在新機(jī)制,。
HIV-1（人類免疫缺陷病毒1型，即艾滋病毒）性傳播主要感染黏膜下層的靶細(xì)胞如CD4+ T細(xì)胞,，而同為性傳播相關(guān)病毒的HSV-2（人類單純皰疹病毒2型）則主要感染黏膜上皮細(xì)胞,。流行病學(xué)數(shù)據(jù)顯示,，HSV-2患者感染HIV-1的機(jī)率增加，但分子機(jī)制不明,。胡勤學(xué)學(xué)科組研究發(fā)現(xiàn),，HSV-2感染人宮頸上皮細(xì)胞后能激活p38-C/EBP-β信號(hào)通路，促使轉(zhuǎn)錄因子C/EBP-β結(jié)合到CXCL9啟動(dòng)子上誘導(dǎo)表達(dá)趨化因子CXCL9,，誘導(dǎo)產(chǎn)生的CXCL9能夠招募HIV-1靶細(xì)胞CD4+ T細(xì)胞,。研究人員據(jù)此提出了HSV-2感染招募大量CD4+ T細(xì)胞至黏膜感染部位，從而增加HIV-1性傳播的潛在分子機(jī)制,。
胡勤學(xué)研究員于2008年底入選中科院項(xiàng)目“百人計(jì)劃”,，2009年作為973首席科學(xué)家申報(bào)獲準(zhǔn)立項(xiàng)“重要病毒的入侵機(jī)制研究”。研究方向?yàn)镠IV-1黏膜感染與免疫,，HSV-2/HIV-1共感染及抑制,。研究成果在J Exp Med， J Infect Dis,， J Immunol,， J Virol， Antimicrob Agents Chemother,， J Mol Biol,， Virology， J Gen Virol及Nature和Nat Med等學(xué)術(shù)期刊上發(fā)表,，其中有些被作為專題評(píng)論,、亮點(diǎn)介紹或期刊封面。研究工作受到973計(jì)劃,、國(guó)家傳染病專項(xiàng),、國(guó)家自然科學(xué)基金、英中合作項(xiàng)目等的資助,。
Faculty of 1000創(chuàng)建于2002年,，評(píng)議成員由上萬(wàn)名國(guó)際知名機(jī)構(gòu)的著名專家組成，根據(jù)論文對(duì)當(dāng)前世界生物和醫(yī)學(xué)研究的貢獻(xiàn)程度和科學(xué)價(jià)值,，推薦收錄極少數(shù)新近發(fā)表的生物和醫(yī)學(xué)論文,，目的是幫助廣大科研人員遴選和發(fā)現(xiàn)有價(jià)值的研究工作。（生物谷Bioon.com）
doi:10.4049/jimmunol.1103706
PMC:
PMID:
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-β Pathway
Wenjie Huang*, Kai Hu*,†, Sukun Luo*,†, Mudan Zhang*,†, Chang Li*,†, Wei Jin*,†, Yalan Liu*, George E. Griffin‡, Robin J. Shattock§ and Qinxue Hu*,‡
Recruitment of CD4+ T cells to infection areas after HSV-2 infection may be one of the mechanisms that account for increased HIV-1 sexual transmission. 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–positive 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-β within CXCL9 promoter sequence. Furthermore, CXCL9 expression is promoted at the transcriptional level through phosphorylating C/EBP-β via p38 MAPK pathway, leading to binding of C/EBP-β 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-β 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-β pathway through promoting the binding of C/EBP-β 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.
