Human immunodeficiency virus type 1 cellular RNA load and splicing patterns predict disease progression in a longitudinally studied cohort.
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.
Michael
N L
NL
Division of Retrovirology, Walter Reed Army Institute of Research, Rockville, Maryland.
Mo
T
T
Merzouki
A
A
O'Shaughnessy
M
M
Oster
C
C
Burke
D S
DS
Redfield
R R
RR
Birx
D L
DL
Cassol
S A
SA
D016915:AIDS Vaccines / Q000276:immunology; D001483:Base Sequence; D018791:CD4 Lymphocyte Count; D017931:DNA Primers / Q000737:chemistry; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000382:microbiology* / Q000473:pathology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008969:Molecular Sequence Data; D011379:Prognosis; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics*; D013997:Time Factors
D016915:AIDS Vaccines; D017931:DNA Primers; D012333:RNA, Messenger; D012367:RNA, Viral