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Blood, 1 January 2002, Vol. 99, No. 1, pp. 88-94
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Correlation of human T-cell lymphotropic virus type 1 (HTLV-1)
mRNA with proviral DNA load, virus-specific CD8+ T cells,
and disease severity in HTLV-1-associated myelopathy
(HAM/TSP)
Yoshihisa Yamano,
Masahiro Nagai,
Meghan Brennan,
Carlos A. Mora,
Samantha S Soldan,
Utano Tomaru,
Norihiro Takenouchi,
Shuji Izumo,
Mitsuhiro Osame, and
Steven Jacobson
From the Viral Immunology Section, Neuroimmunology
Branch, National Institute of Neurological Disorders and Stroke,
National Institutes of Health, Bethesda, MD; Center for Chronic Viral
Diseases, Faculty of Medicine, Kagoshima University, Japan; and Third
Department of Internal Medicine, Faculty of Medicine, Kagoshima
University, Japan.
To investigate the role of viral expression in individuals infected
with human T-cell lymphotropic virus type 1 (HTLV-1), a real-time
quantitative reverse transcription-polymerase chain reaction (RT-PCR)
of HTLV-1 tax messenger RNA (mRNA) using ABI Prism 7700 Sequence Detection System was developed. Using this system, the HTLV-1
tax mRNA load was compared with HTLV-1 proviral DNA load,
HTLV-1 Tax protein expression, HTLV-1 Tax-specific CD8+
T-cell frequency, and disease severity of HTLV-1-associated
myelopathy/tropical spastic paraparesis (HAM/TSP). This approach was a
sensitive and specific technique for the precise quantification of
HTLV-1 tax mRNA. The total amount of HTLV-1 tax
mRNA and mRNA expression level in HTLV-1-infected cells (mRNA/DNA
ratio) were higher in HAM/TSP patients than in asymptomatic HTLV-1
carriers. The HTLV-1 tax mRNA load correlated with the
HTLV-1 proviral DNA load ex vivo, the Tax protein expression in vitro,
and the Tax-specific CD8+ T-cell frequency ex vivo. The
HTLV-1 tax mRNA load also correlated with disease severity
in HAM/TSP patients. These data suggest that increased HTLV-1
expression plays an important role in the pathogenesis of HAM/TSP, and
the HTLV-1 tax mRNA level could be a useful predictor of
disease progression in patients with HAM/TSP.
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