Document 0588
 DOCN  M9550588
 TI    Human immunodeficiency virus type 1 cellular RNA load and splicing
       patterns predict disease progression in a longitudinally studied cohort.
 DT    9505
 AU    Michael NL; Mo T; Merzouki A; O'Shaughnessy M; Oster C; Burke DS;
       Redfield RR; Birx DL; Cassol SA; Division of Retrovirology, Walter Reed
       Army Institute of; Research, Rockville, Maryland.
 SO    J Virol. 1995 Mar;69(3):1868-77. Unique Identifier : AIDSLINE
       MED/95156620
 AB    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.
 DE    AIDS Vaccines/IMMUNOLOGY  Base Sequence  CD4 Lymphocyte Count  DNA
       Primers/CHEMISTRY  *Gene Expression Regulation, Viral  Human  HIV
       Infections/*MICROBIOLOGY/PATHOLOGY  HIV-1/*GENETICS  Longitudinal
       Studies  Molecular Sequence Data  Prognosis  RNA Splicing  RNA,
       Messenger/GENETICS  RNA, Viral/*GENETICS  Time Factors  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).