Novel pathway for induction of latent virus from resting CD4+ T cells in the simian immunodeficiency virus/macaque model of human immunodeficiency virus type 1 latency
Novel pathway for induction of latent virus from resting CD4+ T cells in the simian immunodeficiency virus/macaque model of human immunodeficiency virus type 1 latency
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DOI：
10.1128/jvi.01396-06
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发表时间：
2007-02-01
影响因子：
5.4
通讯作者：
Siliciano, Robert F.
中科院分区：
文献类型：
--
作者：
Shen, Anding;Yang, Hung-Chih;Siliciano, Robert F.
虽然联合治疗可以将人类免疫缺陷病毒1型（HIV-1）病毒血症抑制到无法检测的水平，但由于病毒存在于细胞储库中，特别是静息CD 4（+）T淋巴细胞中的潜伏储库，因此尚未实现根除。我们先前建立了猴免疫缺陷病毒（SIV）/猕猴模型来研究潜伏期。我们在此描述了一种从潜伏感染的静息CD 4（+）T细胞中诱导SIV的新机制。包括CEMx 174和EB病毒转化的人B淋巴母细胞系在内的几种人细胞系介导了静息猕猴T细胞的接触依赖性活化和潜伏性SIV的诱导。抗体阻断试验表明，共刺激分子CD 2及其配体CD 58之间的相互作用参与，而可溶性因子和T细胞受体和主要组织相容性复合体II类之间的相互作用没有。CD 2特异性抗体的组合也诱导携带潜伏HIV-1的人静息CD 4（+）T细胞中的T细胞活化和病毒诱导。这是第一次证明共刺激信号可以在没有T细胞受体共同参与的情况下诱导潜伏病毒，这项研究可能会为靶向潜伏HIV-1的潜在途径提供见解。
Although combination therapy allows the suppression of human immunodeficiency virus type 1 (HIV-1) viremia to undetectable levels, eradication has not been achieved because the virus persists in cellular reservoirs, particularly the latent reservoir in resting CD4(+) T lymphocytes. We previously established a simian immunodeficiency virus (SIV)/macaque model to study latency. We describe here a novel mechanism for the induction of SIV from latently infected resting CD4(+) T cells. Several human cell lines including CEMx174 and Epstein-Barr virus-transformed human B-lymphoblastoid cell lines mediated contact-dependent activation of resting macaque T cells and induction of latent SIV. Antibody-blocking assays showed that interactions between the costimulatory molecule CD2 and its ligand CD58 were involved, whereas soluble factors and interactions between T-cell receptors and major histocompatibility complex class II were not. Combinations of specific antibodies to CD2 also induced T-cell activation and virus induction in human resting CD4(+) T cells carrying latent HIV-1. This is the first demonstration that costimulatory signals can induce latent virus without the coengagement of the T-cell receptor, and this study might provide insights into potential pathways to target latent HIV-1.