Co-infection by lactic dehydrogenase virus and C-type retrovirus elicits neurological disease

Intraperitoneal injection of neuropathogenic strains of lactic dehydrogenase virus (LDV)^1-3 causes a histologically distinctive⁴ fatal paralytic disease characterized by an inflammatory destruction of motor neurones in the brain stem and cord in C58 mice aged over 9 months. To elicit the disease in the naturally susceptible C58 strain requires an age-associated⁵ or X-ray induced⁶ loss of immunological competence⁵, LDV infection^1-3 and genetic susceptibility^1,6. Genetic studies^1,7 of the common inbred mouse strains showed that susceptibility to the disease was not linked to the major histocompatibility complex but correlated with the FV-1ⁿ allele, susceptibility to spontaneous leukaemia, and infection by neuropathogenic strains of LDV^1-3. These observations suggested that neuropathogenic strains of LDV elicit the disease only in those strains of mice that carry multiple copies of N-tropic C-type retroviruses in their genomes^8,9 and that are permissive for retrovirus replication. Presumably the expression of these viral genomes (high titres of virus in tissues correlating with age⁹) is the important factor. Here we present genetic evidence to support this hypothesis and briefly discuss the possible implications.