title: 24 hours in the life of HIV-1 in a T cell line.
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.
authors: Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
authors: Pejman
authors: P
authors: Mohammadi
authors: Sébastien
authors: S
authors: Desfarges
authors: István
authors: I
authors: Bartha
authors: Beda
authors: B
authors: Joos
authors: Nadine
authors: N
authors: Zangger
authors: Miguel
authors: M
authors: Muñoz
authors: Huldrych F
authors: HF
authors: Günthard
authors: Niko
authors: N
authors: Beerenwinkel
authors: Amalio
authors: A
authors: Telenti
authors: Angela
authors: A
authors: Ciuffi
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000502:physiology* / Q000821:virology; D015967:Gene Expression Regulation, Viral; D057809:HEK293 Cells; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D015233:Models, Statistical; D013997:Time Factors; D059467:Transcriptome; D015854:Up-Regulation; D014779:Virus Replication / Q000235:genetics*
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