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.