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.
Division of Retrovirology, Walter Reed Army Institute of Research, Rockville, Maryland.
N L
NL
Michael
T
T
Mo
A
A
Merzouki
M
M
O'Shaughnessy
C
C
Oster
D S
DS
Burke
R R
RR
Redfield
D L
DL
Birx
S A
SA
Cassol
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