Susceptibility of C58 mice to paralytic disease induced by lactate dehydrogenase-elevating virus correlates with increased expression of endogenous retrovirus in motor neurons.
The induction of poliomyelitis by lactate dehydrogenase-elevating virus (LDV) in C58 mice is dependent upon several host factors including old age, loss of immune competence and genetic predisposition. Two genetic components segregate with susceptibility to this neurological disease: the presence of multiple proviral copies of N-tropic endogenous murine leukemia viruses (MuLV) and homozygosity of the permissive allele for N-tropic viral replication (Fv-1n/n). We have quantified the levels of RNA for several endogenous retroviruses, using virus specific oligonucleotide probes, in various tissues of C58 mice in relation to age and immunosuppression. A tissue specific increase in expression of 3.0 kb AKR MuLV RNA in the spinal cords of mice occurred with increasing age of the mice and was enhanced several-fold by immunosuppression in old mice. Susceptibility to LDV-induced poliomyelitis occurs in the same age dependent manner as AKR MuLV expression and is also enhanced by immunosuppression. In contrast, the mink cell focus forming virus (MCF) RNA levels in the spinal cord remained constant despite apparent variations in MCF RNA expression in other tissues, and no xenotropic retrovirus RNA was detectable in spinal cords or brains of the C58 mice. The increased AKR MuLV RNA in the spinal cord was shown by in situ hybridization to be mainly located in the same motor neurons that become infected with LDV in these mice and are destroyed as paralysis develops. These results support a novel dual virus virus hypothesis for LDV-induced poliomyelitis in which increased endogenous retroviral expression in motor neurons renders these cells susceptible to cytocidal replication of LDV and hence to the development of LDV-induced poliomyelitis.
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Department of Microbiology, University of Minnesota Medical School, Minneapolis 55455-0312.
Plagemann
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D000818:Animals; D001483:Base Sequence; D004198:Disease Susceptibility; D007772:Lactate dehydrogenase-elevating virus / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D051379:Mice; D008815:Mice, Inbred Strains / Q000502:physiology*; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000382:microbiology*; D015345:Oligonucleotide Probes; D010243:Paralysis / Q000382:microbiology*; D015183:Restriction Mapping; D013116:Spinal Cord / Q000382:microbiology*
D015345:Oligonucleotide Probes