Binding of HIV-1 virions to α_4β_7 expressing cells and impact of antagonizing α_4β_7 on HIV-1 infection of primary CD4^+ T cells

作     者：Chang Li Wei Jin Tao Du Biao Wu Yalan Liu Robin J Shattock Qinxue Hu 

作者机构：State Key Laboratory of VirologyWuhan Institute of VirologyChinese Academy of Sciences University of Chinese Academy of Sciences Department of General SurgeryWuhan No.1 Hospital Section of Infectious DiseasesFaculty of MedicineImperial College LondonSt.Mary's CampusLondon W21PGUK Institute for Infection and ImmunitySt George’s University of LondonLondon SW170REUK 

出 版 物：《Virologica Sinica》 (中国病毒学（英文版）)

年 卷 期：2014年第29卷第6期

页      面：381-392页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 1001[医学-基础医学(可授医学、理学学位)] 100103[医学-病原生物学] 10[医学] 

基　　金：supported by National Natural Science Foundation of China Grant 81273250 Ministry of Science and Technology of China Grants 2013ZX10001005003-002 and 2012ZX10001006-002 

主　　题：HIV-1 integrin α4β7 binding infection RNA interference primary CD4+ T cells 

摘      要：HIV-1 envelope glycoprotein is reported to interact with α4β7, an integrin mediating the homing of lymphocytes to gut-associated lymphoid tissue, but the significance of α4β7 in HIV-1 infection remains controversial. Here, using HIV-1 strain Ba L, the gp120 of which was previously shown to be capable of interacting with α4β7, we demonstrated that α4β7 can mediate the binding of whole HIV-1 virions to α4β7-expressing transfectants. We further constructed a cell line stably expressing α4β7 and confirmed the α4β7-mediated HIV-1 binding. In primary lymphocytes with activated α4β7 expression, we also observed significant virus binding which can be inhibited by an anti-α4β7 antibody. Moreover, we investigated the impact of antagonizing α4β7 on HIV-1 infection of primary CD4+ T cells. In α4β7-activated CD4+ T cells, both anti-α4β7 antibodies and introduction of shorthairpin RNAs specifically targeting α4β7 resulted in a decreased HIV-1 infection. Our findings indicate that α4β7 may serve as an attachment factor at least for some HIV-1 strains. The established approach provides a promising means for the investigation of other viral strains to understand the potential roles of α4β7 in HIV-1 infection.