HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
BMC Immunol. 2013 Jan 24;14:4. doi: 10.1186/1471-2172-14-4.
It has been shown that human immunodeficiency virus (HIV)-1 infection induces the production of endogenous lipids required for effective viral production, and the cluster of differentiation (CD)1 molecule CD1d is downregulated by HIV-1 infection. However, the role of endogenous lipid presentation and the implications of CD1 downregulation by HIV-1 infection have not yet been characterized.
In this study, we observed downregulation of both CD1c and CD1d expression through a Vpu-dependent and Nef-independent mechanism, and the concomitant HIV-1-induced production of host cholesterol decreased the extent of CD1c and CD1d modulation. While the modest downregulation of CD1c by HIV-1 infection decreased the ability of CD1c-restricted T cells to respond and secrete interferon-γ, the cholesterol upregulation in the same cells by HIV-1 infection appears to limit the downregulation of CD1c.
The two conflicting HIV-1-mediated changes in CD1c expression appear to minimize the modulation of CD1c expression, thus leading the host to maintain a CD1c-restricted T-cell response against HIV-1.
已经证实，人类免疫缺陷病毒（HIV）-1 感染会诱导产生有效病毒产生所需的内源性脂质，并且 CD1 分子 CD1d 会被 HIV-1 感染下调。然而，内源性脂质呈递的作用以及 HIV-1 感染下调 CD1 的意义尚未得到阐明。
在这项研究中，我们观察到 CD1c 和 CD1d 的表达均通过 Vpu 依赖性和 Nef 非依赖性机制下调，同时 HIV-1 诱导的宿主胆固醇产生减少了 CD1c 和 CD1d 调节的程度。虽然 HIV-1 感染导致 CD1c 的适度下调降低了 CD1c 限制性 T 细胞的应答和分泌干扰素-γ的能力，但 HIV-1 感染在相同细胞中上调的胆固醇似乎限制了 CD1c 的下调。
HIV-1 介导的 CD1c 表达的两种相互冲突的变化似乎最大限度地减少了 CD1c 表达的调节，从而使宿主能够维持针对 HIV-1 的 CD1c 限制性 T 细胞应答。
