title: High incidence of HAM/TSP-like symptoms in WKA rats after administration of human T-cell leukemia virus type 1-producing cells.
abstract: We demonstrate a significantly high incidence of human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy (HAM)-or tropical spastic paraparesis (TSP)-like symptoms in WKA rats after injection with HTLV-1-producing MT-2 cells, while no symptoms were observed in F344 rats injected with MT-2 cells or in control WKA rats. Five of the eight (63%) WKA rats injected with MT-2 cells showed HAM/TSP-like paraparesis at 105 weeks of age, but none of seven MT-2-injected F344 rats or eight control WKA rats showed symptoms. This high incidence of HAM/TSP-like symptoms in WKA rats was statistically significant (P < 0.05). Six of the eight (75%) WKA rats injected with MT-2 cells showed HAM/TSP-like paraparesis at 108 weeks of age. HAM/TSP-like symptoms were also observed in one of the two WKA rats injected with HTLV-1-producing Ra-1 cells at 128 weeks of age. HTLV-1 provirus was detected in peripheral blood mononuclear cells in both WKA and F344 rats. The provirus was detected in the spinal cords of the HAM/TSP-like WKA rats that had severe neuropathological changes. WKA and F344 rats showed no significant difference in antibody response against HTLV-1 Gag antigen. However, the antibody response against the C-terminal half of gp46 HTLV-1 envelope protein was lower in WKA rats than in F344 rats. Pathological analysis of the HAM/TSP-like rats showed degeneration of the white matter of the spinal cord and peripheral nerves. These findings suggest that both the genetic background of the host and HTLV-1 infection are important in neuropathogenesis of HAM/TSP-like paraparesis in rats.
authors.affiliation: Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kushida
authors.forename: H
authors.initials: H
authors.lastname: Mizusawa
authors.forename: M
authors.initials: M
authors.lastname: Matsumura
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Ami
authors.forename: M
authors.initials: M
authors.lastname: Hori
authors.forename: K
authors.initials: K
authors.lastname: Yagami
authors.forename: T
authors.initials: T
authors.lastname: Kameyama
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: A
authors.initials: A
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D015481:HTLV-I Antibodies / Q000032:analysis; D015368:Human T-lymphotropic virus 1 / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D015493:Paraparesis, Tropical Spastic / Q000209:etiology* / Q000473:pathology / Q000821:virology; D011533:Proviruses / Q000302:isolation & purification; D011817:Rabbits; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D015481:HTLV-I Antibodies