Document Detail


A doubly fluorescent HIV-1 reporter shows that the majority of integrated HIV-1 is latent shortly after infection.
MedLine Citation:
PMID:  23408629     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
HIV-1 latency poses a major barrier to viral eradication. Canonically, latency is thought to arise from progressive epigenetic silencing of active infections. However, little is known about when and how long terminal repeat (LTR)-silent infections arise since the majority of the current latency models cannot differentiate between initial (LTR-silent) and secondary (progressive silencing) latency. In this study, we constructed and characterized a novel, double-labeled HIV-1 vector (Red-Green-HIV-1 [RGH]) that allows for detection of infected cells independently of LTR activity. Infection of Jurkat T cells and other cell lines with RGH suggests that the majority of integrated proviruses were LTR-silent early postinfection. Furthermore, the LTR-silent infections were transcriptionally competent, as the proviruses could be reactivated by a variety of T cell signaling agonists. Moreover, we used the double-labeled vector system to compare LTRs from seven different subtypes with respect to LTR silencing and reactivation. These experiments indicated that subtype D and F LTRs were more sensitive to silencing, whereas the subtype AE LTR was largely insensitive. Lastly, infection of activated human primary CD4(+) T cells yielded LTR-silent as well as productive infections. Taken together, our data, generated using the newly developed RGH vector as a sensitive tool to analyze HIV-1 latency on a single-cell level, show that the majority of HIV-1 infections are latent early postinfection.
Authors:
Matthew S Dahabieh; Marcel Ooms; Viviana Simon; Ivan Sadowski
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-02-13
Journal Detail:
Title:  Journal of virology     Volume:  87     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-26     Completed Date:  2013-05-15     Revised Date:  2013-10-08    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4716-27     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
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MeSH Terms
Descriptor/Qualifier:
Genes, Reporter
HIV-1 / physiology*
Humans
Jurkat Cells
Staining and Labeling / methods
T-Lymphocytes / virology
Virology / methods
Virus Latency*
Grant Support
ID/Acronym/Agency:
AI064001/AI/NIAID NIH HHS; AI089246/AI/NIAID NIH HHS; AI90935/AI/NIAID NIH HHS; CGD-96495//Canadian Institutes of Health Research; HOP-120237//Canadian Institutes of Health Research; MOP-77807//Canadian Institutes of Health Research; P01 AI090935/AI/NIAID NIH HHS; R01 AI064001/AI/NIAID NIH HHS; R01 AI089246/AI/NIAID NIH HHS
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