Dynamics of HIV-1 mRNA expression in patients with long-term nonprogressive HIV-1 infection

Manola Comar, Cecilia Simonelli, Stefania Zanussi, Paolo De Paoli, Emanuela Vaccher, Umberto Tirelli, Mauro Giacca

Research output: Contribution to journalArticle

Abstract

A large number of evidences indicate that progression of HIV disease is driven by an increase in viral burden. It is still unclear, however, to what extent this is contributed by the dysregulation of the molecular mechanisms governing virus gene expression at the transcriptional or posttranscriptional levels. To address this issue, several quantitative virologic parameters (including provirus transcriptional activity and splicing pattern) were analyzed in individuals with nonprogressive HIV infection and compared with those of a matched group of progressor patients. Exact quantification was achieved by a competitive PCR procedure using a multicompetitor template. Nonprogressors were characterized by striking differences in the levels of viremia, provirus copy number, and overall levels of all viral mRNA classes in peripheral blood mononuclear cells. Additionally, the transcriptional activity of the proviral DNA in these patients was mainly engaged in the production of multiprocessed transcripts, with a pattern resembling the early phases of the experimental infection. Taken together, these results show that both viral load and provirus transcription pattern are remarkably different in infected individuals nonprogressing toward overt disease, and further support the notion that disease progression is accompanied by a change in the kinetics of HIV gene expression.

Original languageEnglish
Pages (from-to)893-903
Number of pages11
JournalJournal of Clinical Investigation
Volume100
Issue number4
Publication statusPublished - Aug 15 1997

Keywords

  • Acquired immunodeficiency syndrome
  • Competitive polymerase chain reaction
  • Pathogenesis
  • Provirus
  • Transcription

ASJC Scopus subject areas

  • Medicine(all)

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    Comar, M., Simonelli, C., Zanussi, S., De Paoli, P., Vaccher, E., Tirelli, U., & Giacca, M. (1997). Dynamics of HIV-1 mRNA expression in patients with long-term nonprogressive HIV-1 infection. Journal of Clinical Investigation, 100(4), 893-903.