Transcriptional Reprogramming during Effector-to-Memory Transition Renders CD4+ T Cells Permissive for Latent HIV-1 Infection
Journal
Immunity
Journal Volume
47
Journal Issue
4
Pages
766-775000
Date Issued
2017
Author(s)
Shan L
Deng K
Gao H
Xing S
Capoferri A.A
Durand C.M
Rabi S.A
Laird G.M
Kim M
Hosmane N.N
Zhang H
Margolick J.B
Li L
Cai W
Ke R
Flavell R.A
Siliciano J.D
Siliciano R.F.
Abstract
The latent reservoir for HIV-1 in resting memory CD4+ T cells is the major barrier to curing HIV-1 infection. Studies of HIV-1 latency have focused on regulation of viral gene expression in cells in which latent infection is established. However, it remains unclear how infection initially becomes latent. Here we described a unique set of properties of CD4+ T cells undergoing effector-to-memory transition including temporary upregulation of CCR5 expression and rapid downregulation of cellular gene transcription. These cells allowed completion of steps in the HIV-1 life cycle through integration but suppressed HIV-1 gene transcription, thus allowing the establishment of latency. CD4+ T cells in this stage were substantially more permissive for HIV-1 latent infection than other CD4+ T cells. Establishment of latent HIV-1 infection in CD4+ T could be inhibited by viral-specific CD8+ T cells, a result with implications for elimination of latent HIV-1 infection by T cell-based vaccines. The latent reservoir for HIV is a barrier to cure, but it is unclear why HIV establishes latency given its ability to evade immune responses through evolution. Shan et al. show that latency is an unfortunate consequence of infection of CD4+ T cells within a narrow time window after activation. ? 2017
SDGs
Other Subjects
CD38 antigen; CD45RO antigen; chemokine receptor CCR5; chemokine receptor CXCR4; gamma interferon; green fluorescent protein; interleukin 10; interleukin 13; interleukin 2; interleukin 2 receptor alpha; interleukin 5; interleukin 8; Ki 67 antigen; protein bcl 2; tumor necrosis factor; virus DNA; cytokine; Article; CD4+ T lymphocyte; cell transformation; controlled study; cytokine production; down regulation; effector cell; effector to memory transitioning; ex vivo study; female; gene expression; genetic transcription; genetic transfection; human; human cell; Human immunodeficiency virus 1 infection; in vitro study; latent virus infection; long terminal repeat; male; memory cell; microarray analysis; priority journal; reverse transcription; T lymphoblast; T lymphocyte activation; transient expression; upregulation; virus entry; virus envelope; virus replication; CD4+ T lymphocyte; cell culture; cytotoxic T lymphocyte; flow cytometry; gene expression profiling; genetic transcription; genetics; host pathogen interaction; Human immunodeficiency virus 1; immunological memory; immunology; lymphocyte activation; metabolism; nuclear reprogramming; physiology; procedures; reverse transcription polymerase chain reaction; virology; virus latency; CD4-Positive T-Lymphocytes; Cells, Cultured; Cellular Reprogramming; Cytokines; Female; Flow Cytometry; Gene Expression Profiling; HIV-1; Host-Pathogen Interactions; Humans; Immunologic Memory; Lymphocyte Activation; Male; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes, Cytotoxic; Transcription, Genetic; Virus Latency; Virus Replication
Publisher
Cell Press
Type
journal article