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).
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.
Yamano
Yoshihisa
Y
Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Nagai
Masahiro
M
Brennan
Meghan
M
Mora
Carlos A
CA
Soldan
Samantha S
SS
Tomaru
Utano
U
Takenouchi
Norihiro
N
Izumo
Shuji
S
Osame
Mitsuhiro
M
Jacobson
Steven
S
D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology* / Q000821:virology; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D015870:Gene Expression; D016356:Gene Products, tax / Q000235:genetics / Q000276:immunology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000276:immunology / Q000821:virology*; D011533:Proviruses / Q000235:genetics*; D012333:RNA, Messenger / Q000097:blood; D012367:RNA, Viral / Q000097:blood*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019562:Viral Load
D004279:DNA, Viral; D016356:Gene Products, tax; D012333:RNA, Messenger; D012367:RNA, Viral