Age-dependent paraparesis in WKA rats: evaluation of MHC k-haplotype and HTLV-1 infection.
Human T-cell leukemia virus type 1 (HTLV-1) infection is shown to be closely associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although the occurrence of HAM/TSP was reported to be associated with MHC class II, the mechanism is still unclear. The WKA(RT1k) strain of rats was reported to develop HAM/TSP-like paraparesis after HTLV-1 infection, and was suggested to be an animal model of HAM/TSP. We asked whether MHC k-haplotype is specifically involved in the pathogenesis of paraparesis of WKA(RT1k) rats. We injected the HTLV-1 producing human T cells (MT-2 cells) intravenously into WKA(RT1k) rats and MHC congenic WKA.1L(RT1l) rats which have MHC l-haplotype of LEW rats on the WKA background. Positive antibody response to HTLV-1 antigens and presence of provirus in peripheral blood mononuclear cells confirmed that MT-2 cell-injected rats were infected with HTLV-1. Two of 13 MT-2 cell-injected WKA(RT1k) rats and five of 13 MT-2 cell-injected WKA.1L(RT1l) rats developed HAM/TSP-like hindlimb paraparesis between 16 and 26 months old. Interestingly, three of 14 MT-2 cell-uninjected WKA(RT1k) rats and four of 13 MT-2 cell-uninjected WKA.1L(RT1l) rats showed similar paraparesis between 15 and 26 months old. MHC k-haplotype is not specific to the development of paraparesis in WKA(RT1k) rats. The role of aging, genetic background, HTLV-1 infection and other factors on the development of HAM/TSP-like paraparesis in rats are discussed.
Sun
B
B
Department of Biochemistry and Molecular Oncology, Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Japan.
Fang
J
J
Yagami
K
K
Kushida
S
S
Tanaka
M
M
Uchida
K
K
Miwa
M
M
D000367:Age Factors; D000483:Alleles; D000818:Animals; D005260:Female; D005802:Genes, MHC Class II / Q000235:genetics*; D015490:HTLV-I Infections / Q000150:complications / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D020335:Paraparesis / Q000209:etiology / Q000235:genetics*; D051381:Rats