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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Authors: | Shen Anding Yang Hung-Chih Zhou Yan Chase Amanda J Boyer Jean D Zhang Hao Margolick Joseph B Zink M Christine Clements Janice E Siliciano Robert F |
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Affiliation: | Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. as28@calvin.edu |
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Abstract: | 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. |
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