Productive measles virus brain infection and apoptosis in CD46 transgenic mice

Measles virus (MV) infection causes acute childhood disease, associated in certain cases with infection of the central nervous system (CNS) and develo pment of neurological disease. To develop a murine model of MV-induced path ology, we generated several Lines of transgenic mice ubiquitously expressin g as the MV receptor a human CD46 molecule with either a Cyt1 or Cyt2 cytop lasmic tail. All transgenic lines expressed CD46 protein in the brain. Newb orn transgenic mice, in contrast to nontransgenic controls, were highly sen sitive to intracerebral infection by the MV Edmonston strain. Signs of clin ical illness (lack of mobility, tremors, and weight loss) appeared within 5 to 7 days after infection, followed by seizures, paralysis, and death of t he infected animals. Virus replication was detected in neurons from infecte d mice, and virus was reproducibly isolated from transgenic brain tissue. M V-induced apoptosis observed in different brain regions preceded the death of infected animals. Similar results were obtained with mice expressing eit her a Cyt1 or Cyt2 cytoplasmic tail, demonstrating the ability of different isoforms of CD46 to function as MV receptors in vivo. In addition, materna lly transferred immunity delayed death of offspring given a lethal dose of MV, These results document a novel CD46 transgenic murine model where MV ne uronal infection is associated with the production of infectious virus, sim ilarly to progressive infectious measles encephalitis seen in immunocomprom ised patients, and provide a new means to study pathogenesis of MV infectio n in the CNS.