Mouse hepatitis virus type 4 (JHM strains). induced fatal central nervous system disease. I. genetic control and murine neuron as the susceptible site of disease

Occurs Infrequently in Neuronal Cells. To evaluate replication of MHV in vivo SJL/J and BALB/c mice were inoculated intracerebrally with 100 BALB/c LDso of virus, and after killing at various intervals, their tissues were assayed for amounts of infectious virus. Virus replicated to some degree in SJL/J brains, but the titers were 100-to 1,000-fold lower than in BALB/c mice tested within the first 2 d after inoculation (Table III) . Thereafter, the majority of BALB/c mice died, but surviving SJL/J mice consistently had lower titers of virus than BALB/c mice killed during the peak of infection. Virus replicated to higher titers, 1 to 3 logs more, in CNS tissues (brain and spinal cord) than in livers, spleens, or thymuses. Again, virus titers were significantly higher in all tissues from BALB/c mice when compared with those from SJL/J mice. Virus replication in inoculated BALB/WEHI mice were equivalent to that seen in BALB/c mice. The use of a specific fixative and unembedded sections thinly sliced with a vibratome enabled us to preserve sufficient viral antigen and morphologic structure to assess the CNS cell type involved and the sites of antigen localization (Fig. 1) . The study of spinal cord and brain tissue from BALB/c mice showed evidence of MHV-4 antigen expression both in neurons (Fig. 1) and in glial cells. To the contrary, it was uncommon to find MHV-4 antigens in neuronal cells of SJL/J mice. However, when the viral dose was increased 100-fold, occasional neuronal cells from SJL/J mice contained M H V antigens.