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

Intraperitoneal injection of neuropathogenic strains of lactic dehydrogenase virus (LDV) causes a histologically distinctive 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-associated or X-ray induced loss of immunological competence, LDV infection and genetic susceptibility. Genetic studies 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. 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 and that are permissive for retrovirus replication. Presumably the expression of these viral genomes (high titres of virus in tissues correlating with age) is the important factor. Here we present genetic evidence to support this hypothesis and briefly discuss the possible implications.