Microbial Pathogenesis 1989; 6: 391-401 Mini-review Dual virus etiology of age-dependent poliomyelitis of mice. A potential model for human motor neuron diseases Christopher H. Contag, John T. Harty and Peter G. W. Plagemann Department of Microbiology, University of Minnesota, Medical School, 420 Delaware Street S.E., Minneapolis, Minnesota 55455-0372, U.S.A. Multifactorial etiology of age-dependent poliomyelitis {ADPM) A number of human motor neuron diseases exhibit complex etiologies, perhaps involving viruses.’ Progress in resolving these etiologies has been impeded by the lack of suitable animal models. One potential model is the motor neuron disease ADPM, which is associated with infections of certain mouse strains with lactate dehydro- genase-elevating virus (LDV).‘-a Recent studies of ADPM have led to a novel concept of neuropathogenesis, which involves the interaction of two viruses in motor neuron destruction. ADPM exhibits certain similarities to amyotrophic lateral sclerosis (ALS) of humansg-” in that susceptibility to both diseases is age-related, associated with multiple genetic and environmental factors and that the pathology is limited to anterior horn motor neurons. The factors involved in susceptibility have not been identified as yet for ALS, but have been largely elucidated for ADPM. Susceptibility of mice to ADPM has been genetically linked to the presence of multiple proviral copies of N-tropic, ecotropic murine leukemia virus (MLV) and homozygosity of the allele at the locus that permits the replication of N-tropic MLV (Fv-1 ni”).3,5 This genetic background is typically found in high leukemic mouse strains such as AKR and C58.3s5 Susceptibility of these mice increases with increasing age and is enhanced in old mice by cyclophosphamide treatment or X-irradiation.2,3 For example, C58/M mice 10 months of age or older are ~90% susceptible to ADPM, whereas less than 50% of 5-8-month-old mice develop paralytic disease after LDV infection. However, the incidence of the disease is increased to nearly 100% if 5-8- month-old mice are treated with cyclophosphamide (200 mg/kg) or X-irradiated (600 rads) l-2 days prior to LDV infection. 2,3,5*12,‘3 Two-month-old C58/M remain asymptomatic after LDV infection regardless of whether or not they have been treated with cyclophosphamide or X-irradiation.2,3,5*‘2,‘3 H owever, susceptibility to ADPM varies considerably among different colonies of C58 and AKR mice. C58/J mice are less susceptible than C58/M mice; only a small proportion of 6-7-month-old C58/J mice develop paralytic symptoms after infection with a neuropathogenic strain of LDV, even after pretreatment with cyclophosphamide’2f’3 Similarly, 6-7-month-old AKR/Boy mice are nearly 100% susceptible to ADPM, whereas AKR/J mice of similar age appear to be resistant.5,‘2s’4 The basis for the differences among these colonies has not been resolved, but could be related to differences in ecotropic retrovirus expression in these mice (see later). Paralytic symptoms in susceptible mice generally appear 2-3 weeks p.i. with a 0882-4010/89/060391+11 SOS.OO/O @ 1989 Academic Press Limited