Development of recombinant canine distemper virus and their biochemical and cell biological characterization in vitro

Abstract

Morbilliviruses are enveloped negative-strand RNA viruses that cause severe disease in their respective hosts. Pathogenesis studies of measles virus (MeV) in nonhuman primates and canine distemper virus (CDV) in ferrets reveal that wild-type strains initially target immune cells and then spread to epithelia and in some cases to the central nervous system. Upon aerosol transmission, these viruses initially target signaling lymphocyte activation. Molecule (SLAM; CD150)-expressing immune cells in the respiratory tract, followed by dissemination throughout the lymphatic system. SLAM proteins from different host species serve as receptors for multiple morbilliviruses. The importance of immune cell targeting for the establishment of morbillivirus infection is illustrated by the complete attenuation of SLAM binding-defective MeV and CDV in vivo despite their ability to infect and replicate in non-immune cells as efficiently as wild type viruses in vitro. Because of the more severe disease caused by CDV in ferrets, this animal model is ideal to characterize the morbillivirus pathogenesis mechanisms. (AU)