Sequence heterogeneity of HTLV-I proviral DNA in the central nervous system of patients with HTLV-I-associated myelopathy.
The nucleotide sequence of human T-lymphotropic virus type I (HTLV-I) in central nervous system tissue was determined in 3 autopsy cases 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. The pX-defective mutants found frequently in the central nervous system 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.
Kira
J
J
Department of Neurology, Kyushu University, Fukuoka, Japan.
Koyanagi
Y
Y
Yamada
T
T
Itoyama
Y
Y
Tateishi
J
J
Akizuki
S
S
Kishikawa
M
M
Baba
E
E
Nakamura
M
M
Suzuki
J
J
D000368:Aged; D001483:Base Sequence; D002493:Central Nervous System Diseases / Q000209:etiology / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D015686:Gene Products, env / Q000235:genetics; D016355:Genes, pX / Q000235:genetics; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000209:etiology / Q000235:genetics; D009154:Mutation; D016366:Open Reading Frames / Q000235:genetics; D015493:Paraparesis, Tropical Spastic / Q000150:complications / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000235:genetics
D004279:DNA, Viral; D015686:Gene Products, env