HERV-K-specific T cells eliminate diverse HIV-1/2 and SIV primary isolates
HERV-K-specific T cells eliminate diverse HIV-1/2 and SIV primary isolates
复制标题
DOI：
10.1172/jci64560
复制
发表时间：
2012-12-01
影响因子：
15.9
通讯作者：
Ostrowski, Mario A.
中科院分区：
文献类型：
--
作者：
Jones, R. Brad;Garrison, Keith E.;Ostrowski, Mario A.
HIV-1的遗传多样性代表了疫苗发育中的主要挑战。在这项研究中，我们通过针对稳定的人体内源性逆转录病毒（HERV）抗原来靶向细胞免疫反应来消除HIV-1感染细胞。人类基因组中的HERV DNA序列代表了古代感染性逆转录病毒的残留物。我们表明，用HIV-1的CD4（+）T细胞感染导致HERV型K型HML-2谱系的转录[HERV-K（HML-2）]和GAG和ENV蛋白的表达。 HERV-K（HML-2） - 特异性CD8（+）T细胞从HIV-1感染的人类受试者获得的，在体外以VIF依赖性方式对HIV-1感染的细胞反应。与所提出的作用方式一致，HERV-K（HML-2）特异性CD8（+）T细胞克隆表现出全球多样的HIV-1，HIV-1，HIV-1和SIV分离株感染的细胞的全面消除。体外。我们确定了第二个T细胞反应，该反应表现出同源HIV-1-POL和HERV-K（HML-2） - pol的决定因素之间的交叉反应性，从而提高了HIV-1和HERV之间的同源性在塑造和塑造中起作用的可能性也许增强了T细胞对HIV-1的反应。这证明了HERV-K（HML-2）特异性和交叉反应T细胞反应在HIV-1感染的自然控制中以及探索HERV-K（HML-2）靶向的HIV-1疫苗和不寻常的治疗剂。
The genetic diversity of HIV-1 represents a major challenge in vaccine development. In this study, we establish a rationale for eliminating HIV-1-infected cells by targeting cellular immune responses against stable human endogenous retroviral (HERV) antigens. HERV DNA sequences in the human genome represent the remnants of ancient infectious retroviruses. We show that the infection of CD4(+) T cells with HIV-1 resulted in transcription of the HML-2 lineage of HERV type K [HERV-K(HML-2)] and the expression of Gag and Env proteins. HERV-K(HML-2)-specific CD8(+) T cells obtained from HIV-1-infected human subjects responded to HIV-1-infected cells in a Vif-dependent manner in vitro. Consistent with the proposed mode of action, a HERV-K(HML-2)-specific CD8(+) T cell clone exhibited comprehensive elimination of cells infected with a panel of globally diverse HIV-1, HIV-2, and SIV isolates in vitro. We identified a second T cell response that exhibited cross-reactivity between homologous HIV-1-Pol and HERV-K(HML-2)-Pol determinants, raising the possibility that homology between HIV-1 and HERVs plays a role in shaping, and perhaps enhancing, the T cell response to HIV-1. This justifies the consideration of HERV-K(HML-2)-specific and cross-reactive T cell responses in the natural control of HIV-1 infection and for exploring HERV-K(HML-2)-targeted HIV-1 vaccines and inununotherapeutics.