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 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. DOI: https://doi.org/10.1371/journal.ppat.1003161 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-81662 Published Version Originally published at: Mohammadi, Pejman; Desfarges, Sébastien; Bartha, István; Joos, Beda; Zangger, Nadine; Muñoz, Miguel; Günthard, Huldrych F; Beerenwinkel, Niko; Telenti, Amalio; Ciuffi, Angela (2013). 24 hours in the life of HIV-1 in a T cell line. PLoS Pathogens, 9(1):e1003161. DOI: https://doi.org/10.1371/journal.ppat.1003161 24 Hours in the Life of HIV-1 in a T Cell Line Pejman Mohammadi, Sébastien Desfarges, István Bartha, Beda Joos, Nadine Zangger, Miguel Muñoz, Huldrych F. Günthard, Niko Beerenwinkel*, Amalio Telenti*, Angela Ciuffi* 1 Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland, 2 SIB Swiss Institute of Bioinformatics, Basel and Lausanne, Switzerland, 3 Institute of Microbiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, 4 Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, 5 University of Lausanne, Lausanne, Switzerland