| Project/Area Number |
05670562
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
KIRA Junichi Kyushu Univ.Medicine, lecturer, 医学部, 講師 (40183305)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1993: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | HTLV-I / HTLV-I-associated myelopathy / polymerase chain reaction / central nervous system / anti-HTLV-I antibodies / mutation / tax / rex / ヒトT細胞性白血病ウイルス / HTLV-I / HTLV-I-associated myelopathy / pX / proviral DNA |
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| Research Abstract |
The nucleotide sequence of human T-lymphotropic virus type I (HTLV-I) in central nervous system tissue was determined in 3 autopsy case with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) and 1 seropositive carrier without HAM/TSP but with multiple sclerosis. All HAM/TSP samples (3 spinal cords and 2 brains) and the sample from the seropositive carrier without HAM/TSP (brain) were positive for HTLV-I env (5146-6681), pX5'(6549-7494), and pX3'(7354-8276) regions by the two-step polymerase chain reaction method. A nucleotide sequence analysis of the pX5' and pX3' polymerase chain reaction products from nucleotides 6631 to 8259 revealed heterogeneity of the HTLV-I genome in all cases. It is notable that 13 of 50 clones derived from the pX3' polymerase chain reaction products were defective in the tax open reading frame while 7 were defective in the rex open reading frame in the HAM/TSP samples. All 17 clones from 1 HAM/TSP case were defective in the pX open reading frame II.One nucleotide insertion at 7784 creating a frame shift in both tax and rex was seen in all 3 HAM/TSP cases but not in the HTLV-I carrier without HAM/TSP.In order to examine the possibilty of the expression of the mutant tax protein in vivo, we determined the serum antibody titers to the synthetic peptides corresponding to the new amino acid sequence created by the nucleotide insertion at 7784 by enzyme-linked immunosorbent assay. The antibody against the mutanttax peptide was positive in 11 of 43 HAM patients, while it was positive only in 2 of 25 HTLV-I-seropositive carriers without HAM and negative in 40 HTLV-I-seronegative subjects. The pX-defective mutants found frequently in the central nervous system are likely to be expressed in vivo and may contribute to the neural damage, since the pX gene products are essential for the transactivation of various cellular genes as well as for viral replication.
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