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.
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.
Shen
Anding
A
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. as28@calvin.edu
Yang
Hung-Chih
HC
Zhou
Yan
Y
Chase
Amanda J
AJ
Boyer
Jean D
JD
Zhang
Hao
H
Margolick
Joseph B
JB
Zink
M Christine
MC
Clements
Janice E
JE
Siliciano
Robert F
RF
D000818:Animals; D018801:CD2 Antigens / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D018968:CD58 Antigens / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear; D008251:Macaca; D023421:Models, Animal; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D017735:Virus Latency
D018801:CD2 Antigens; D018968:CD58 Antigens