24 Hours in the Life of HIV-1 in a T Cell Line

PLoS Pathogens

Pejman Mohammadi¹  Angela Ciuffi¹  Nadine Zangger²  Amalio Telenti²  Niko Beerenwinkel³  Huldrych F. Günthard³  István Bartha³  Beda Joos³  Miguel Muñoz⁴  Sébastien Desfarges⁴ 

[1] Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland;Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland;Institute of Microbiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland;SIB Swiss Institute of Bioinformatics, Basel and Lausanne, Switzerland

关键词: Gene expression;    HIV-1;    Transcriptome analysis;    Life cycles;    Viral replication;    MicroRNAs;    RNA sequencing;    Primary cells;   

DOI  :  10.1371/journal.ppat.1003161

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY