ANALYSIS OF THE MOLECULAR-BASIS OF NEUROPATHOGENESIS OF RNA VIRUSES IN EXPERIMENTAL-ANIMALS - RELEVANCE FOR HUMAN-DISEASE

RNA viruses with segmented genomes were the first model used for molec ular analysis of viral neuropathogenesis, since they could be analysed genetically by reassortment. Four viruses with non-segmented genomes have been used as models of neurovirulence and demyelinating disease: JHM coronavirus, Theiler's virus, Sindbis virus and Semliki Forest vir us (SFV). Virus gene expression in the central nervous system of infec ted animals has been measured by in situ hybridization and immunocytoc hemistry. Cell tropism has been analysed by neural cell culture. Infec tious clones have been constructed for Theiler's virus, Sindbis virus and SFV, and these allow analysis of the sequences involved in the det ermination of neuropathogenesis, through the construction of chimeric viruses and site-specific mutagenesis. Measles and rubella viruses hav e been studied in animal systems because of their importance for human disease. The importance of two recently discovered mechanisms of neur opathogenesis, antibody-induced modulation of virus multiplication, an d persistence of virus in the absence of multiplication, remains to be assessed.