Sequence heterogeneity of HTLV-I proviral DNA in the central nervous system of patients with HTLV-I–associated myelopathy

✍ Scribed by Dr. Jun-ichi Kira; Yoshio Koyanagi; Takeshi Yamada; Yasuto Itoyama; Jun Tateishi; Shin-ichiro Akizuki; Masao Kishikawa; Eishi Baba; Minoru Nakamura; Jun Suzuki; Tatsufumi Nakamura; Naomi Nakamura; Naoki Yamamoto; Ikuo Goto

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 774 KB
• Volume: 36
• Category: Article
• ISSN: 0364-5134
• DOI: 10.1002/ana.410360206

✦ Synopsis

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 HAMiTSP (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 HAMlTSP case were defective in the pX open reading frame 11. One nucleotide insertion at 7784 creating a frame shift in both tax and rex was seen in all 3 HAMlTSP 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.