Herpes Simplex Virus Type 2 Infection-Induced Expression of CXCR3 Ligands Promotes CD4(+) T Cell Migration and Is Regulated by the Viral Immediate-Early Protein ICP4

doi:10.3389/fimmu.2018.02932

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	Herpes Simplex Virus Type 2 Infection-Induced Expression of CXCR3 Ligands Promotes CD4(+) T Cell Migration and Is Regulated by the Viral Immediate-Early Protein ICP4
	Hu, Qinxue 1,4; Gong, Sitang 2; Liu, Yalan 4; Li, Mei 3,4; Hu, Kai 4; Hu, Huimin 3,4; Chen, Rui 4; Zhang, Binman 3,4; Fu, Ming 3,4; Geng, Lanlan 2
刊名	FRONTIERS IN IMMUNOLOGY
	2018-12-19
卷号	9 页码:15
关键词	HSV-2 CXCR3 ligands CD4(+) T cells recruitment ICP4
ISSN号	1664-3224
DOI	10.3389/fimmu.2018.02932
英文摘要	HSV-2 infection-induced CXCR3 ligands are important for the recruitment of virus-specific CD8(+) T cells, but their impact on CD4(+) T cell trafficking remains to be further determined. Given that recruitment of CD4(+) T cells to infection areas may be one of the mechanisms that account for HSV-2 infection-mediated enhancement of HIV-1 sexual transmission, here we investigated the functionality of HSV-2 infection-induced CXCR3 ligands CXCL9, CXCL10, and CXCL11 in vivo and in vitro, and determined the viral components responsive for such induction and the underlying mechanisms. We first found that the expression of CXCR3 ligands CXCL9, CXCL10, and CXCL11 was increased in mice following vaginal challenge with HSV-2, while CXCL9 played a predominant role in the recruitment of CD4(+) T cells to the vaginal foci of infected mice. HSV-2 infection also induced the production of CXCL9, CXCL10, and CXCL11 in human cervical epithelial cells. Of note, although HSV-2 induced the expression of all the three CXCR3 ligands, the induced CXCL9 appeared to play a predominant role in promoting CD4(+) T cell migration, reflecting that the concentrations of CXCL10 and CXCL11 required for CD4(+) T cell migration are higher than that of CXCL9. We further revealed that, ICP4, an immediate-early protein of HSV-2, is crucial in promoting CXCR3 ligand expression through the activation of p38 MAPK pathway. Mechanistically, ICP4 binds to corresponding promoters of CXCR3 ligands via interacting with the TATA binding protein (TBP), resulting in the transcriptional activation of the corresponding promoters. Taken together, our study highlights HSV-2 ICP4 as a vital viral protein in promoting CXCR3 ligand expression and CXCL9 as the key induced chemokine in mediating CD4(+) T cell migration. Findings in this study have shed light on HSV-2 induced leukocyte recruitment which may be important for understanding HSV-2 infection- enhanced HIV-1 sexual transmission and the development of intervention strategies.
资助项目	National Natural Science Foundation of China[81572009] ; State Key Laboratory of Virology[klv-2016-02]
WOS研究方向	Immunology
语种	英语
出版者	FRONTIERS MEDIA SA
WOS记录号	WOS:000453868400001
内容类型	期刊论文
源URL	[http://202.127.146.157/handle/2RYDP1HH/6385]
专题	中国科学院武汉植物园
通讯作者	Hu, Qinxue; Gong, Sitang
作者单位	1.St Georges Univ London, Inst Infect & Immun, London, England 2.Guangzhou Med Univ, Dept Gastroenterol, Guangzhou Women & Childrens Med Ctr, Guangzhou, Guangdong, Peoples R China 3.Univ Chinese Acad Sci, Beijing, Peoples R China 4.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan, Hubei, Peoples R China 5.Chinese Acad Sci, Wuhan Inst Virol, Guangzhou Inst Pediat, Joint Ctr Translat Precis Med,Guangzhou Women & C, Wuhan, Hubei, Peoples R China
推荐引用方式 GB/T 7714	Hu, Qinxue,Gong, Sitang,Liu, Yalan,et al. Herpes Simplex Virus Type 2 Infection-Induced Expression of CXCR3 Ligands Promotes CD4(+) T Cell Migration and Is Regulated by the Viral Immediate-Early Protein ICP4[J]. FRONTIERS IN IMMUNOLOGY,2018,9:15.
APA	Hu, Qinxue.,Gong, Sitang.,Liu, Yalan.,Li, Mei.,Hu, Kai.,...&Zhang, Di.(2018).Herpes Simplex Virus Type 2 Infection-Induced Expression of CXCR3 Ligands Promotes CD4(+) T Cell Migration and Is Regulated by the Viral Immediate-Early Protein ICP4.FRONTIERS IN IMMUNOLOGY,9,15.
MLA	Hu, Qinxue,et al."Herpes Simplex Virus Type 2 Infection-Induced Expression of CXCR3 Ligands Promotes CD4(+) T Cell Migration and Is Regulated by the Viral Immediate-Early Protein ICP4".FRONTIERS IN IMMUNOLOGY 9(2018):15.