ROLE OF THE GENETIC BACKGROUND OF RATS IN INFECTION BY HTLV-I AND HTLV-II AND IN THE DEVELOPMENT OF ASSOCIATED DISEASES

Three aspects of the rat model of HTLV-I/II infection were investigate d. (i) The efficacy of HTLV-I-transformed rat cell lines in infecting different strains of rats: WKY and Lewis HTLV-I-transformed cell lines were injected into adult WKY, Lewis and Brown Norway rats, representi ng syngeneic and allogeneic combinations. The HTLV-I provirus was not detected in peripheral-blood mononuclear cells (PBMC) from these rats is weeks after inoculation, showing that HTLV-I-transformed rat cells are not suitable for virus challenge in vaccination experiments, Rats inoculated with Lewis HTLV-I-transformed cells produced an antibody re sponse to HTLV-I, which was higher in allogeneic (WKY and Brown Norway ) than in syngeneic rats. (ii) The susceptibility of rats to HTLV-II i nfection: After human HTLV-II-producing cells (MO) were injected into adult WKY rats, the HTLV-II provirus was detected in PBMC 12 weeks lat er, Sequencing of a portion of this provirus confirmed its identity wi th the HTLV-II from MO cells. (iii) The role of MHC haplotype in susce ptibility to neurological disease in rats inoculated as newborns with HTLV-I: The hypothesis that the RT-I-k haplotype confers susceptibilit y was tested by inoculating newborn OKA (RT-I-k), WKY (RT-I-l), Lewis (RT-I-l) and Fischer 344 (RT-I-lvl) rats with human HTLV-I-producing c ells (MT-2), Eighteen months later, only the WKY rats showed histologi cal abnormality of the spinal cord, without clinical paralysis. Fische r 344 rats developed cutaneous tumors and OKA rats mammary tumors. The HTLV-I provirus was not detected in these tumors. (C) 1997 Wiley-Liss , Inc.