HIV Reactivation in Latently Infected Cells with Virological Synapse-Like Cell Contact
HIV Reactivation in Latently Infected Cells with Virological Synapse-Like Cell Contact
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DOI：
10.3390/v12040417
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发表时间：
2020-04-01
期刊：
影响因子：
4.7
通讯作者：
Morikawa, Yuko
中科院分区：
文献类型：
--
作者：
Okutomi, Toshiki;Minakawa, Satoko;Morikawa, Yuko
HIV从潜伏期重新激活是由细胞因子诱导的，也是由细胞与其他细胞接触引起的。为了更好地理解这一点，J1.1细胞，一种潜伏的HIV-1感染Jurkat衍生物，与其亲本Jurkat共同培养。仅当J1.1细胞与刺激的Jurkat细胞接触时，J1.1细胞才呈p17MA阳性，并产生高水平的HIV p24CA抗原。相反，当它们在没有细胞接触的情况下共培养时，几乎没有产生p24CA。潜伏的ACH-2细胞与其亲本A3.01细胞共培养也得到类似的结果。共聚焦显微镜显示，不仅HIV-1p17MA和gp120Env在细胞接触部位聚集，而且LFA-1、CD81、CD59和TCRCD3也聚集在细胞接触部位，表明形成了病毒学突触样结构。LFA-1-ICAM-1参与细胞间的相互作用。当J1.1与TCR缺失的Jurkat共培养时，p17MA阳性率显著降低，但细胞与细胞之间的接触并未受到损害。定量蛋白质组学鉴定了54个膜分子，其中一个是MHC I类分子，聚集在细胞接触部位。潜伏期的重新激活也受基质细胞存在的影响。我们的研究表明，J1.1/ACH-2细胞中潜伏的HIV-1可以通过与刺激亲本细胞的细胞间接触而有效地重新激活，并伴随着病毒学突触样结构。
HIV reactivation from latency is induced by cytokines but also by cell contact with other cells. To better understand this, J1.1 cells, a latent HIV-1-infected Jurkat derivative, were cocultured with its parental Jurkat. J1.1 cells became p17MA-positive and produced a high level of HIV p24CA antigen, only when they were cocultured with stimulated Jurkat with cell-to-cell contact. In contrast, very little p24CA was produced when they were cocultured without cell contact. Similar results were obtained when latent ACH-2 and its parental A3.01 cells were cocultured. Confocal microscopy revealed that not only HIV-1 p17MA and gp120Env but also LFA-1, CD81, CD59, and TCR CD3 accumulated at the cell contact site, suggesting formation of the virological synapse-like structure. LFA-1-ICAM-1 interaction was involved in the cell-to-cell contact. When J1.1 was cocultured with TCR-deficient Jurkat, the p17MA-positive rate was significantly lower, although the cell-to-cell contact was not impaired. Quantitative proteomics identified 54 membrane molecules, one of which was MHC class I, that accumulated at the cell contact site. Reactivation from latency was also influenced by the presence of stromal cells. Our study indicated that latent HIV-1 in J1.1/ACH-2 cells was efficiently reactivated by cell-to-cell contact with stimulated parental cells, accompanying the virological synapse-like structure.