近日，Faculty of 1000收录和点评了中科院武汉病毒研究所胡勤学学科组发表在The Journal of Immunology（2012 Jun 15；188(12)：6247-57）上的HSV-2和HIV-1黏膜共感染论文，认为该研究发现提出了HSV-2感染增加HIV-1黏膜传播的潜在新机制。
HIV-1（人类免疫缺陷病毒1型，即艾滋病毒）性传播主要感染黏膜下层的靶细胞如CD4+ T细胞，而同为性传播相关病毒的HSV-2（人类单纯疱疹病毒2型）则主要感染黏膜上皮细胞。流行病学数据显示，HSV-2患者感染HIV-1的机率增加，但分子机制不明。胡勤学学科组研究发现，HSV-2感染人宫颈上皮细胞后能激活p38-C/EBP-β信号通路，促使转录因子C/EBP-β结合到CXCL9启动子上诱导表达趋化因子CXCL9，诱导产生的CXCL9能够招募HIV-1靶细胞CD4+ T细胞。研究人员据此提出了HSV-2感染招募大量CD4+ T细胞至黏膜感染部位，从而增加HIV-1性传播的潜在分子机制。
胡勤学研究员于2008年底入选中科院项目“百人计划”，2009年作为973首席科学家申报获准立项“重要病毒的入侵机制研究”。研究方向为HIV-1黏膜感染与免疫，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等学术期刊上发表，其中有些被作为专题评论、亮点介绍或期刊封面。研究工作受到973计划、国家传染病专项、国家自然科学基金、英中合作项目等的资助。
Faculty of 1000创建于2002年，评议成员由上万名国际知名机构的著名专家组成，根据论文对当前世界生物和医学研究的贡献程度和科学价值，推荐收录极少数新近发表的生物和医学论文，目的是帮助广大科研人员遴选和发现有价值的研究工作。（生物谷Bioon.com）
doi:10.4049/jimmunol.1103706
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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.
