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Title

Residual cell-associated unspliced HIV-1 RNA in peripheral blood of patients on potent antiretroviral therapy represents intracellular transcripts

Authors
Fischer, Marek
Wong, J. K.
Russenberger, Doris
Joos, Beda
Opravil, Milos
Trkola, Alexandra
Kuster, Herbert
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Published in Antiviral Therapy. 2002, vol. 7, no. 2, p. 91-103
Abstract Unspliced HIV-RNA (HIV-UsRNA) associated with peripheral blood mononuclear cells (PBMCs) persists in patients on potent antiretroviral therapy even in the absence of detectable plasma HIV-RNA. To further characterize such residual HIV-RNA, cell-associated virion-encapsidated HIV and intracellular unspliced HIV-RNA were differentiated and monitored using a novel highly sensitive method. In addition, expression of HIV-mRNA encoding tat and rev was assessed. PBMCs of patients with unsuppressed plasma viraemia harboured an extracellular fraction of HIV-UsRNA, which correlated highly with intracellular HIV-RNA levels. Thus, extracellular PBMC-associated HIV-RNA may, to a significant extent, reflect nascent virions attached to productively infected cells. Upon treatment with potent antiretroviral therapy resulting in plasma viraemia <50 copies/ml, expression of cell-associated viral particles was hardly discernible in PBMCs but transcription of unspliced HIV-RNA persisted. Given the virtual absence of rev-mRNA, translation of residual HIV-UsRNA was probably precluded by retention of these transcripts in the nucleus. As shown by limiting dilution analysis, HIV-1 infected cells with such a repressed viral transcription pattern were observed at high frequencies in PBMC from untreated patients.
Keywords Anti-HIV Agents/ therapeutic useCell LineCohort StudiesGenes, revGenes, tatHIV Infections/blood/ drug therapy/virologyHIV-1/ geneticsHumansLeukocytes, Mononuclear/ virologyRNA, Messenger/analysisRNA, Viral/ blood
Identifiers
PMID: 12212929
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FISCHER, Marek et al. Residual cell-associated unspliced HIV-1 RNA in peripheral blood of patients on potent antiretroviral therapy represents intracellular transcripts. In: Antiviral Therapy, 2002, vol. 7, n° 2, p. 91-103. https://archive-ouverte.unige.ch/unige:7216

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Deposited on : 2010-06-21

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