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

被引:122
作者
Mohammadi, Pejman [1 ,2 ,3 ]
Desfarges, Sebastien [4 ]
Bartha, Istvan [4 ]
Joos, Beda [5 ]
Zangger, Nadine [2 ,3 ,4 ]
Munoz, Miguel [4 ]
Guenthard, Huldrych F. [5 ]
Beerenwinkel, Niko [1 ,2 ,3 ]
Telenti, Amalio [4 ,6 ]
Ciuffi, Angela [4 ,6 ]
机构
[1] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland
[2] SIB, Basel, Switzerland
[3] SIB, Lausanne, Switzerland
[4] CHU Vaudois, Inst Microbiol, CH-1011 Lausanne, Switzerland
[5] Univ Zurich, Div Infect Dis & Hosp Epidemiol, Univ Zurich Hosp, Zurich, Switzerland
[6] Univ Lausanne, Lausanne, Switzerland
基金
瑞士国家科学基金会;
关键词
LEVEL;
D O I
10.1371/journal.ppat.1003161
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
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.
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页数:11
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