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

Anding Shen, Hung Chih Yang, Yan Zhou, Amanda J. Chase, Jean D. Boyer, Hao Zhang, Joseph Bernard Margolick, Mary Christine Zink, Janice E Clements, Robert F Siliciano

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1660-1670
Number of pages11
JournalJournal of Virology
Volume81
Issue number4
DOIs
StatePublished - Feb 2007

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ASJC Scopus subject areas

  • Immunology

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