Human immunodeficiency virus type 1 cellular RNA load and splicing patterns predict disease progression in a longitudinally studied cohort

J Virol. 1995 Mar;69(3):1868-77. doi: 10.1128/JVI.69.3.1868-1877.1995.

Abstract

We report the results of a longitudinal study of RNA splicing patterns in 31 early-stage human immunodeficiency virus disease patients with an average follow-up time of 3 years. Eighteen patients showed no evidence for disease progression, whereas 13 patients either showed a > or = 50% reduction in baseline CD4 count or developed opportunistic infections. Levels of unspliced, tat, rev, and nef mRNAs in peripheral blood mononuclear cells were measured by a reverse transcriptase-quantitative, competitive PCR assay. Viral RNA was detected in all patients at all time points. All 13 rapid progressors had viral RNA loads that were > or = 1 log unit greater than those of the slow progressors. In addition, seven of the rapid progressors showed a reduction of more than threefold in the ratio of spliced to unspliced RNA over the 3 years of follow-up. Conversely, two slow progressors with intermediate levels of viral RNA showed no splicing shift. These results confirm earlier observations that viral RNA is uniformly expressed in early-stage patients. We further show that cellular RNA viral load is predictive of disease progression. Importantly, the shift from a predominately spliced or regulatory viral mRNA pattern to a predominately unspliced pattern both is associated with disease progression and adds predictive utility to measurement of either RNA class alone.

MeSH terms

  • AIDS Vaccines / immunology
  • Base Sequence
  • CD4 Lymphocyte Count
  • DNA Primers / chemistry
  • Gene Expression Regulation, Viral*
  • HIV Infections / microbiology*
  • HIV Infections / pathology
  • HIV-1 / genetics*
  • Humans
  • Longitudinal Studies
  • Molecular Sequence Data
  • Prognosis
  • RNA Splicing
  • RNA, Messenger / genetics
  • RNA, Viral / genetics*
  • Time Factors

Substances

  • AIDS Vaccines
  • DNA Primers
  • RNA, Messenger
  • RNA, Viral