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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Virus Latency
Simian immunodeficiency virus
Virus Activation
Simian Immunodeficiency Virus
Macaca
Human immunodeficiency virus 1
HIV-1
T-lymphocytes
T-Lymphocytes
viruses
T-Cell Antigen Receptor
Viruses
Cell Line
Blocking Antibodies
Viremia
Major Histocompatibility Complex
Human Herpesvirus 4
Human herpesvirus 4
receptors
antibodies

ASJC Scopus subject areas

  • Immunology

Cite this

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title = "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",
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.",
author = "Anding Shen and Yang, {Hung Chih} and Yan Zhou and Chase, {Amanda J.} and Boyer, {Jean D.} and Hao Zhang and Margolick, {Joseph Bernard} and Zink, {Mary Christine} and Clements, {Janice E} and Siliciano, {Robert F}",
year = "2007",
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T1 - 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

AU - Shen, Anding

AU - Yang, Hung Chih

AU - Zhou, Yan

AU - Chase, Amanda J.

AU - Boyer, Jean D.

AU - Zhang, Hao

AU - Margolick, Joseph Bernard

AU - Zink, Mary Christine

AU - Clements, Janice E

AU - Siliciano, Robert F

PY - 2007/2

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