Li Chang, Jin Wei, Du Tao, Wu Biao, Liu Yalan, Shattock Robin J, Hu Qinxue
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.
Virol Sin. 2014 Dec;29(6):381-92. doi: 10.1007/s12250-014-3525-8. Epub 2014 Dec 10.
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 BaL, 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 short-hairpin 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.
据报道,HIV-1包膜糖蛋白与α4β7相互作用,α4β7是一种整合素,介导淋巴细胞归巢至肠道相关淋巴组织,但α4β7在HIV-1感染中的意义仍存在争议。在此,我们使用HIV-1 BaL毒株(其gp120先前已证明能够与α4β7相互作用),证明α4β7可介导完整HIV-1病毒体与表达α4β7的转染子结合。我们进一步构建了稳定表达α4β7的细胞系,并证实了α4β7介导的HIV-1结合。在α4β7表达激活的原代淋巴细胞中,我们也观察到显著的病毒结合,且这种结合可被抗α4β7抗体抑制。此外,我们研究了拮抗α4β7对原代CD4(+) T细胞HIV-1感染的影响。在α4β7激活的CD4(+) T细胞中,抗α4β7抗体和引入特异性靶向α4β7的短发夹RNA均导致HIV-1感染减少。我们的研究结果表明,α4β7可能至少对某些HIV-1毒株起到附着因子的作用。所建立的方法为研究其他病毒株以了解α4β7在HIV-1感染中的潜在作用提供了一种有前景的手段。