DYNAMICS OF HIV-1 MESSENGER-RNA EXPRESSION IN PATIENTS WITH LONG-TERMNONPROGRESSIVE HIV-1 INFECTION

A large number of evidences indicate that progression of HIV disease i s driven by an increase in viral burden. It is still unclear, however, to what extent this is contributed by the dysregulation of the molecu lar mechanisms governing virus gene expression at the transcriptional or posttranscriptional levels. To address this issue, several quantita tive virologic parameters (including provirus transcriptional activity and splicing pattern) were analyzed in individuals with nonprogressiv e HIV infection and compared with those of a matched group of progress or patients. Exact quantification was achieved by a competitive PCR pr ocedure using a multicompetitor template. Nonprogressors were characte rized by striking differences in the levels of viremia, provirus copy number, and overall levels of all viral mRNA classes in peripheral blo od mononuclear cells. Additionally, the transcriptional activity of th e proviral DNA in these patients was mainly engaged in the production of multiprocessed transcripts, with a pattern resembling the early pha ses 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 accompani ed by a change in the kinetics of HIV gene expression.