Thewidespread presenceofendogenous retroviruses inthegenomesofanimals andhumanshassuggested thatthese viruses may beinvolved inbothnormalandabnormal developmental processes. Previous studies haveindicated theinvolvement ofendogenous ecotropic murineleukemia virus(MuLV)inthedevelopment of age-dependent poliomyelitis causedbyinfection ofoldC58or AKR micebylactate dehydrogenase-elevating virus (LDV). Theonlygenetic components whichsegregate withsusceptibility toLDV-induced paralytic disease aremultiple proviral copies ofecotropic MuLV andthepermissive allele, attheFv-1locus, forN-tropic, ecotropic virus replication (Fv-_nln). Using insituhybridization andNorthern (RNA)blothybridization, we havecorrelated theexpression oftheendogenous MuLV,bothtemporally andspatially, withLDV infection of anterior hornmotorneurons andthedevelopment ofparalysis. Ourdataindicate thattreatment of6-to 7-month-old C58/Mmicewithcyclophosphamide, whichrenders thesemicesusceptible toLDV-induced paralytic disease, results intransient increases inecotropic MuLV RNA levels inmotorneuronsthroughout the spinal cord. Peripheral inoculation ofC58/MmicewithLDV,atthetimeofelevated MuLV RNA levels, results ina rapidspread ofLDV tosome spinal cordmotorneurons.LDV infections thenspread slowly but progressively throughout thespinal cord, involving an increasing numberofmotorneurons.LDV replication iscytocidal andresults inneurondestruction andparalysis oftheinfected animals 2to3weekspostinfection. Theslowreplication ofLDV inthespinal cordcontrasts sharply withtherapidreplication ofLDV in macrophages, thenormalhostcells forLDV,during theacutephase ofinfection. Thedataindicate thatthe interaction between theendogenous MuLV withthegenerally nonpathogenic murinetogavirus LDV occursat thelevel ofthemotorneuron. We discuss potential mechanisms forthenoveldual-virus etiology of age-dependent poliomyelitis ofmice.
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