Abstract
Measles virus (MeV), the causative agent of measles, can persist in the brain and cause a fatal neurodegenerative disease, subacute sclerosing panencephalitis (SSPE). Because wild-type MeV is not neurotropic, the virus is thought to evolve and acquire neuropathogenicity to cause SSPE. Our recent studies have shown that MeV acquires hyperfusogenic mutations in the fusion (F) gene that confer the ability to use cell adhesion molecule 1 (CADM1) and CADM2 as cis-acting receptor mimicking molecules and allow MeV to spread in neurons. Furthermore, under these conditions, multiple MeV genomes, rather than a single one, are likely to be transmitted transsynaptically between neurons through cell-cell fusion. Therefore, F proteins encoded by different genomes are co-expressed in infected cells, and positive and negative functional interactions between them can occur. These interactions determine the ability of the virus to spread in neurons as a population. In this article, we describe our studies to understand the mechanism by which MeV acquires neuropathogenicity in SSPE.
