Mouse hepatitis virus (MHV) is a prevalent, highly contagious coronavirus with significant impact on the research usefulness of infected mice. The MHV group, like other coronaviruses, contains strains with primary respiratory or enterotropism. The overall objective of this project is to critically examine the pathogenesis of enterotropic MHV, which is the least studied but most common form of Information gained from these studies will have direct practical relevance to accurate diagnosis, control and management of MHV in laboratory mouse populations.
Specific aims of this project include examination of host age and genotype related differentials in susceptibility, duration and response to infection; the role of intestinal mucosal proliferative kinetics in host susceptibility and response; mechanisms of dissemination of virus from intestine to other organs; maternally-derived passive immunity to infection; and virus strain specificity of host challenge immunity. These studies will involve inoculation (:)f BALB/cByJ, SJL/J and other mouse genotypes wit'-. MHV at 2 days and 1,2,3 or 12 weeks of age. Host responses will be examined at intervals after infection. Methodology to assess infection will include histology, MHV immunohistochemistry, mucosal proliferative kinetics (including autoradiography), infectious virus detection and quantification, viral nucleic acid hybridization and serology (IgA, IgG and IgM responses). Data generated from these studies will not only be relevant to laboratory mice, but will also serve to define MHV as a useful general model of coronaviral enteritis, a widespread and important cause of neonatal disease in man and animals.
