Dynamics and modulation of human immunodeficiency virus type 1 transcripts in vitro and in vivo

Patrizia Bagnarelli, Anna Valenza, Stefano Menzo, Riccardo Sampaolesi, Pietro E. Varaldo, Luca Butini, Maria Montroni, Carlo Federico Perno, Stefano Aquaro, Dominique Mathez, Jacques Leibowitch, Claudia Balotta, Massimo Clementi

Research output: Contribution to journalArticlepeer-review

Abstract

The dynamics of human immunodeficiency virus type 1 (HIV-1) transcription was analyzed in vitro and in vivo by using a specific molecular approach which allows accurate quantitation of the different classes of viral mRNAs. Unspliced (US) and multiply spliced (MS) HIV-1 transcripts were assayed by competitive reverse transcription (cRT)-PCR, using a single competitor RNA bearing in tandem internally deleted sequences of both template species. Acute HIV-1 infection of primary peripheral blood mononuclear cells (PBMCs), monocytes/macrophages cells, and the A3.01 T- lymphocyte-derived cell line was studied; both classes of HIV-1 mRNAs increased exponentially (r2 > 11.98) at days 1 to 3 and 1 to 4 postinfection in HIV(IIIB)-infected A3.01 cells and PBMCs, respectively, whereas monocytes/macrophages infected with monocytotropic HIV(BaL) exhibited a linear (r2 = 0.81 to 0.94) accumulation of US and MS transcripts. Following induction of chronically infected ACH-2 cells, MS transcripts increased 2 h postinduction and peaked at 5 h (doubling time, 58 min), while at 24 h, US mRNAs increased 3.053-fold compared with basal time (doubling time, 137 min). To address the biopathological significance of HIV-1 expression pattern during infection progression, pilot cross-sectional and longitudinal analyses were carried out with samples from untreated and treated HIV-l-infected patients. In almost all untreated (recently infected, long-term nonprogressor, and progressor) patients, MS transcript levels followed the general trend of systemic HIV-1 activity. In patients under treatment with powerful antiretroviral compounds, viral MS transcripts rapidly fell to undetectable levels, indicating that in vivo, levels of MS mRNAs in PBMCs are closely associated with the number of newly infected cells and suggesting a new role for the quantitative analysis of HIV-1 transcription in infected patients.

Original languageEnglish
Pages (from-to)7603-7613
Number of pages11
JournalJournal of Virology
Volume70
Issue number11
Publication statusPublished - Nov 1996

ASJC Scopus subject areas

  • Immunology

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