HIV-1 infection ex vivoaccelerates measles virus infection by upregulating signaling lymphocytic activation molecule (SLAM) in CD4+T cells
HIV-1 infection ex vivoaccelerates measles virus infection by upregulating signaling lymphocytic activation molecule (SLAM) in CD4+T cells
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HIV-1 体外感染通过上调 CD4 T 细胞中的信号淋巴细胞激活分子 (SLAM) 加速麻疹病毒感染
DOI：
10.1128/jvi.06681-11
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发表时间：
2012
期刊：
影响因子：
5.4
通讯作者：
Tsunetsugu-Yokota Y
中科院分区：
文献类型：
--
作者：
Mitsuki Y;Terahara K;Shibusawa K;Yamamoto T;Tsuchiya T;Ishige M;Kobayashi K;Morikawa Y;Nakayama T;Takeda M;Yanagi Y;Tsunetsugu-Yokota Y
携带人类免疫缺陷病毒1型（HIV-1）的儿童麻疹病毒（MV）感染通常是致命的，即使在中和抗体的存在下;然而，其潜在机制尚不清楚。因此，本研究的目的是检查HIV-1和野生型MV（MVwt）或MV疫苗株（MVvac）在双重感染期间的相互作用。结果表明，MVwt-和MVvac-感染的CD 4 +T细胞的频率在静止的外周血单个核细胞（PBMC）增加3- 4倍后，HIV-1感染，这是与一个显着上调信号淋巴细胞活化分子（SLAM）的CD 4 +T细胞的表达，但不是在CD 8 +T细胞。SLAM上调由包含X4和R5型的复制能力HIV-1分离株感染诱导，并在较小程度上由假型HIV-1感染诱导。值得注意的是，在HIV感染的以及未感染的CD 4 +T细胞中观察到SLAM上调，并且通过从PBMC培养物中去除HLA-DR+细胞而消除。此外，SLAM上调没有发生在未感染的PBMC与HIV感染的PBMC一起培养在由渗透膜隔开的隔室中，表明没有可溶性因子参与。相反，通过白细胞功能相关分子1（LFA-1）/细胞间粘附分子1（ICAM-1）和LFA-3/CD 2与树突状细胞直接接触介导的CD 4 +T细胞活化至关重要。因此，HIV-1感染诱导CD 4 +T细胞上高水平的SLAM表达，这可能会增强其对MV的易感性，并加重合并感染个体的麻疹。
Measles virus (MV) infection in children harboring human immunodeficiency virus type 1 (HIV-1) is often fatal, even in the presence of neutralizing antibodies; however, the underlying mechanisms are unclear. Therefore, the aim of the present study was to examine the interaction between HIV-1 and wild-type MV (MVwt) or an MV vaccine strain (MVvac) during dual infection. The results showed that the frequencies of MVwt- and MVvac-infected CD4+T cells within the resting peripheral blood mononuclear cells (PBMCs) were increased 3- to 4-fold after HIV-1 infection, and this was associated with a marked upregulation of signaling lymphocytic activation molecule (SLAM) expression on CD4+T cells but not on CD8+T cells. SLAM upregulation was induced by infection with a replication-competent HIV-1 isolate comprising both the X4 and R5 types and to a lesser extent by a pseudotyped HIV-1 infection. Notably, SLAM upregulation was observed in HIV-infected as well as -uninfected CD4+T cells and was abrogated by the removal of HLA-DR+cells from the PBMC culture. Furthermore, SLAM upregulation did not occur in uninfected PBMCs cultured together with HIV-infected PBMCs in compartments separated by a permeable membrane, indicating that no soluble factors were involved. Rather, CD4+T cell activation mediated through direct contact with dendritic cells via leukocyte function-associated molecule 1 (LFA-1)/intercellular adhesion molecule 1 (ICAM-1) and LFA-3/CD2 was critical. Thus, HIV-1 infection induces a high level of SLAM expression on CD4+T cells, which may enhance their susceptibility to MV and exacerbate measles in coinfected individuals.