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24 hours in the life of HIV-1 in a T cell line.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2013
Author Mohammadi Pejman, Desfarges Sébastien, Bartha István, Joos Beda, Zangger Nadine, Muñoz Miguel, Günthard Huldrych F, Beerenwinkel Niko, Telenti Amalio, Ciuffi Angela,
Project Host evolutionary genomics of HIV-1 and other retroviruses
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Original article (peer-reviewed)

Journal PLoS pathogens
Volume (Issue) 9(1)
Page(s) 1003161 - 1003161
Title of proceedings PLoS pathogens
DOI 10.1371/journal.ppat.1003161

Open Access

URL http://www.ncbi.nlm.nih.gov/pubmed/23382686
Type of Open Access Website

Abstract

HIV-1 infects CD4+ T cells and completes its replication cycle in approximately 24 hours. We employed repeated measurements in a standardized cell system and rigorous mathematical modeling to characterize the emergence of the viral replication intermediates and their impact on the cellular transcriptional response with high temporal resolution. We observed 7,991 (73%) of the 10,958 expressed genes to be modulated in concordance with key steps of viral replication. Fifty-two percent of the overall variability in the host transcriptome was explained by linear regression on the viral life cycle. This profound perturbation of cellular physiology was investigated in the light of several regulatory mechanisms, including transcription factors, miRNAs, host-pathogen interaction, and proviral integration. Key features were validated in primary CD4+ T cells, and with viral constructs using alternative entry strategies. We propose a model of early massive cellular shutdown and progressive upregulation of the cellular machinery to complete the viral life cycle.
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