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

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 transcrip...

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Main Authors: Pejman Mohammadi, Sébastien Desfarges, István Bartha, Beda Joos, Nadine Zangger, Miguel Muñoz, Huldrych F Günthard, Niko Beerenwinkel, Amalio Telenti, Angela Ciuffi
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS Pathogens
Online Access:http://europepmc.org/articles/PMC3561177?pdf=render
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author Pejman Mohammadi
Sébastien Desfarges
István Bartha
Beda Joos
Nadine Zangger
Miguel Muñoz
Huldrych F Günthard
Niko Beerenwinkel
Amalio Telenti
Angela Ciuffi
author_facet Pejman Mohammadi
Sébastien Desfarges
István Bartha
Beda Joos
Nadine Zangger
Miguel Muñoz
Huldrych F Günthard
Niko Beerenwinkel
Amalio Telenti
Angela Ciuffi
author_sort Pejman Mohammadi
collection DOAJ
description 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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spelling doaj.art-3c2a7340926c4c58824cb6570af541142022-12-22T01:30:00ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742013-01-0191e100316110.1371/journal.ppat.100316124 hours in the life of HIV-1 in a T cell line.Pejman MohammadiSébastien DesfargesIstván BarthaBeda JoosNadine ZanggerMiguel MuñozHuldrych F GünthardNiko BeerenwinkelAmalio TelentiAngela CiuffiHIV-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.http://europepmc.org/articles/PMC3561177?pdf=render
spellingShingle Pejman Mohammadi
Sébastien Desfarges
István Bartha
Beda Joos
Nadine Zangger
Miguel Muñoz
Huldrych F Günthard
Niko Beerenwinkel
Amalio Telenti
Angela Ciuffi
24 hours in the life of HIV-1 in a T cell line.
PLoS Pathogens
title 24 hours in the life of HIV-1 in a T cell line.
title_full 24 hours in the life of HIV-1 in a T cell line.
title_fullStr 24 hours in the life of HIV-1 in a T cell line.
title_full_unstemmed 24 hours in the life of HIV-1 in a T cell line.
title_short 24 hours in the life of HIV-1 in a T cell line.
title_sort 24 hours in the life of hiv 1 in a t cell line
url http://europepmc.org/articles/PMC3561177?pdf=render
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