High incidence of HAM/TSP-like symptoms in WKA rats after administration of human T-cell leukemia virus type 1-producing cells

Shigeki Kushida, Hidehiro Mizusawa, Masayuki Matsumura, Hiroko Tanaka, Yoshihiro Ami, Mitsuo Hori, Ken Ichi Yagami, Tsuneo Kameyama, Yuetsu Tanaka, Atsushi Yoshida, Hiroshi Nyunoya, Kunitada Shimotohno, Yuzo Iwasaki, Kazuhiko Uchida, Masanao Miwa

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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.

Original languageEnglish
Pages (from-to)7221-7226
Number of pages6
JournalJournal of Virology
Volume68
Issue number11
Publication statusPublished - 1994 Nov
Externally publishedYes

Fingerprint

Primate T-lymphotropic virus 1
Deltaretrovirus
Tropical Spastic Paraparesis
Human T-lymphotropic virus 1
Spinal Cord Diseases
incidence
Incidence
rats
Inbred F344 Rats
Paraparesis
cells
Proviruses
proviruses
Antibody Formation
Spinal Cord
Viral Envelope Proteins
spinal cord
gag Gene Products
Spinal Nerves
Virus Diseases

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Kushida, S., Mizusawa, H., Matsumura, M., Tanaka, H., Ami, Y., Hori, M., ... Miwa, M. (1994). High incidence of HAM/TSP-like symptoms in WKA rats after administration of human T-cell leukemia virus type 1-producing cells. Journal of Virology, 68(11), 7221-7226.

High incidence of HAM/TSP-like symptoms in WKA rats after administration of human T-cell leukemia virus type 1-producing cells. / Kushida, Shigeki; Mizusawa, Hidehiro; Matsumura, Masayuki; Tanaka, Hiroko; Ami, Yoshihiro; Hori, Mitsuo; Yagami, Ken Ichi; Kameyama, Tsuneo; Tanaka, Yuetsu; Yoshida, Atsushi; Nyunoya, Hiroshi; Shimotohno, Kunitada; Iwasaki, Yuzo; Uchida, Kazuhiko; Miwa, Masanao.

In: Journal of Virology, Vol. 68, No. 11, 11.1994, p. 7221-7226.

Research output: Contribution to journalArticle

Kushida, S, Mizusawa, H, Matsumura, M, Tanaka, H, Ami, Y, Hori, M, Yagami, KI, Kameyama, T, Tanaka, Y, Yoshida, A, Nyunoya, H, Shimotohno, K, Iwasaki, Y, Uchida, K & Miwa, M 1994, 'High incidence of HAM/TSP-like symptoms in WKA rats after administration of human T-cell leukemia virus type 1-producing cells', Journal of Virology, vol. 68, no. 11, pp. 7221-7226.
Kushida S, Mizusawa H, Matsumura M, Tanaka H, Ami Y, Hori M et al. High incidence of HAM/TSP-like symptoms in WKA rats after administration of human T-cell leukemia virus type 1-producing cells. Journal of Virology. 1994 Nov;68(11):7221-7226.
Kushida, Shigeki ; Mizusawa, Hidehiro ; Matsumura, Masayuki ; Tanaka, Hiroko ; Ami, Yoshihiro ; Hori, Mitsuo ; Yagami, Ken Ichi ; Kameyama, Tsuneo ; Tanaka, Yuetsu ; Yoshida, Atsushi ; Nyunoya, Hiroshi ; Shimotohno, Kunitada ; Iwasaki, Yuzo ; Uchida, Kazuhiko ; Miwa, Masanao. / High incidence of HAM/TSP-like symptoms in WKA rats after administration of human T-cell leukemia virus type 1-producing cells. In: Journal of Virology. 1994 ; Vol. 68, No. 11. pp. 7221-7226.
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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.",
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AU - Ami, Yoshihiro

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AU - Yagami, Ken Ichi

AU - Kameyama, Tsuneo

AU - Tanaka, Yuetsu

AU - Yoshida, Atsushi

AU - Nyunoya, Hiroshi

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AU - Iwasaki, Yuzo

AU - Uchida, Kazuhiko

AU - Miwa, Masanao

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N2 - 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.

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