Binding of HIV-1 virions to α4β7 expressing cells and impact of antagonizing α4β7 on HIV-1 infection of primary CD4+ T cells |
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作者姓名: | Chang Li Wei Jin Tao Du Biao Wu Yalan Liu Robin J Shattock Qinxue Hu |
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作者单位: | State Key Laboratory of Virology,Wuhan Institute of Virology,Chinese Academy of Sciences;University of Chinese Academy of Sciences;Department of General Surgery,Wuhan No.1 Hospital;Section of Infectious Diseases,Faculty of Medicine,Imperial College London,St.Mary’s Campus,London W21PG,UK;Institute for Infection and Immunity,St George’s University of London,London SW170RE,UK |
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基金项目: | supported by National Natural Science Foundation of China Grant 81273250;Ministry of Science and Technology of China Grants 2013ZX10001005003-002 and 2012ZX10001006-002 |
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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.
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关 键 词: | HIV-1 integrin α4β7 binding infection RNA interference primary CD4+ T cells |
收稿时间: | 2014-10-21 |
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