Nov 20, 2013

Quantifying the turnover of transcriptional subclasses of HIV-1-infected cells

BioRxiv : the Preprint Server for Biology
Christian L AlthausHuldrych F Günthard

Abstract

Background HIV-1-infected cells in peripheral blood can be grouped into different transcriptional subclasses. Quantifying the turnover of these cellular subclasses can provide important insights into the viral life cycle and the generation and maintenance of latently infected cells. Results We used previously published data from five patients chronically infected with HIV-1 that initiated combination antiretroviral therapy (cART). Patient-matched PCR for unspliced and multiply spliced viral RNAs combined with limiting dilution analysis provided measurements of transcriptional profiles at the single cell level. Furthermore, measurement of intracellular transcripts and extracellular virion-enclosed HIV-1 RNA allowed us to distinguish productive from non-productive cells. We developed a mathematical model describing the dynamics of plasma virus and the transcriptional subclasses of HIV-1-infected cells. Fitting the model to the data allowed us to better understand the phenotype of different transcriptional subclasses and their contribution to the overall turnover of HIV-1 before and during cART. The average number of virus-producing cells in peripheral blood is small during chronic infection (25.7 cells ml − 1). We find that 14.0...Continue Reading

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Mentioned in this Paper

Study
In Vivo
Human immunodeficiency virus 1 RNA
Virus
Extracellular
Peripheral Blood
Virion
Protoplasm
Transcription, Genetic
Genes, Viral

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