Retrovirus-induced spongiform encephalopathy: the 3'-end long terminal repeat-containing viral sequences influence the incidence of the disease and the specificity of the neurological syndrome.
Using chimeric murine leukemia viruses (MuLVs) constructed in vitro with parental viral genomes from the neurotropic Cas-BR-E MuLV and the nonneurotropic amphotropic 4070-A MuLV, we previously mapped the paralysis-inducing determinant of Cas-BR-E MuLV within a pol-env region. To assess the role of the long terminal repeats (LTRs) in influencing the neurological disease, we constructed another chimeric MuLV (pNEMO-1)m harboring the gag-pol-env from Cas-BR-E MuLV and the LTR region from the strongly T-cell tropic Moloney MuLV. Although the Cas-BR-E MuLV induced mainly nonthymic leukemia, pNEMO-1 MuLV induced a thymic form of leukemia, as the parental Moloney MuLV. The pNEMO-1 MuLV induced neurological diseases less frequently than Cas-BR-E MuLV when inoculated intraperitoneally into NIH/Swiss, SIM.S, and SWR/J mice. However, it induced neurological disorders more frequently and with a shorter latency than Cas-BR-E MuLV when inoculated intrathymically. Most mice with a neurological disorder induced with pNEMO-1 MuLV showed a new clinical syndrome not usually seen with the parental Cas-BR-E MuLV: They had no lower limb paralysis but were excessively tremulous, spastic, and immobile. The topographical distribution of the spongiform degeneration in the brain of mice with this new syndrome was different from that seen in mice with lower limb paralysis induced by Cas-BR-E MuLV. These results indicate that the 1.0-kilobase-pair Cla I-Pvu I LTR-containing fragment harbors sequences influencing the incidence and the clinical manifestation of the neurological disease and suggest a specificity of LTR sequences for a new tissue (brain).
D000818:Animals; D001483:Base Sequence; D001927:Brain Diseases / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D004279:DNA, Viral / Q000235:genetics; D007942:Leukemia, Experimental / Q000382:microbiology; D051379:Mice; D008979:Moloney murine leukemia virus / Q000235:genetics / Q000472:pathogenicity*; D010243:Paralysis / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D010957:Plasmids; D012091:Repetitive Sequences, Nucleic Acid
D004279:DNA, Viral