Type I interferons suppress viral replication but contribute to T cell depletion and dysfunction during chronic HIV-1 infection
Type I interferons suppress viral replication but contribute to T cell depletion and dysfunction during chronic HIV-1 infection
复制标题
DOI：
10.1172/jci.insight.94366
复制
发表时间：
2017-06-15
期刊：
影响因子：
8
通讯作者：
Su, Lishan
中科院分区：
文献类型：
--
作者：
Cheng, Liang;Yu, Haisheng;Su, Lishan
在慢性感染期间，持续I型干扰素（IFN-I）信号传导与hiv -1诱导的免疫发病机制之间的直接联系尚不清楚。在此，我们报告了在人源化小鼠（hu-小鼠）持续感染HIV-1期间使用单克隆抗体阻断ifn - α / β受体1 （IFNAR1）信号传导的研究。我们发现，在慢性HIV-1感染期间，IFNAR阻断增加了病毒复制，这与T细胞激活升高相关。因此，IFN-Is在慢性期抑制HIV-1的复制，但对HIV-1诱导的异常免疫激活不是必需的。令人惊讶的是，尽管HIV-1复制和免疫激活升高，IFNAR阻断术挽救了总人类T细胞和hiv特异性T细胞数量。我们发现IFNAR阻断可减少hiv -1诱导的CD4(+) T细胞凋亡。重要的是，IFNAR阻断也挽救了人类T细胞的功能，包括hiv -1特异性CD8（+）和CD4(+) T细胞。我们得出结论，在持续的HIV-1感染期间，IFN-Is抑制HIV-1复制，但有助于T细胞的耗竭和功能障碍。
The direct link between sustained type I interferon (IFN-I) signaling and HIV-1-induced immunopathogenesis during chronic infection remains unclear. Here we report studies using a monoclonal antibody to block IFN-alpha/beta receptor 1 (IFNAR1) signaling during persistent HIV-1 infection in humanized mice (hu-mice). We discovered that, during chronic HIV-1 infection, IFNAR blockade increased viral replication, which was correlated with elevated T cell activation. Thus, IFN-Is suppress HIV-1 replication during the chronic phase but are not essential for HIV-1-induced aberrant immune activation. Surprisingly, IFNAR blockade rescued both total human T cell and HIV-specific T cell numbers despite elevated HIV-1 replication and immune activation. We showed that IFNAR blockade reduced HIV-1-induced apoptosis of CD4(+) T cells. Importantly, IFNAR blockade also rescued the function of human T cells, including HIV-1-specific CD8(+) and CD4(+) T cells. We conclude that during persistent HIV-1 infection, IFN-Is suppress HIV-1 replication, but contribute to depletion and dysfunction of T cells.