Reverse Genetics System for Measles Virus: Establishment and Applications for Analysis of Virus Replication and Pathogenesis

Abstract

In 1990 Kobune et al. succeeded in isolating pathogenic wild-type strains of measles virus (MV) using a marmoset B-lymphoblastoid cell line B95a. Their data indicated that MV strains that have been used in laboratories are attenuated strains through the adaptation to grow in a variety of cultured cells. We have established a very efficient reverse genetics system that allows us to engineer the genome of a wild-type MV strain at will by site-directed mutagenesis or recombination. Using the system it was shown that (1) the H protein determines tropism of MV, (2) the M protein regulates mode of MV spread, (3) the C protein inhibits host innate immune responses, and (4) the long untranslated regions in the M and F genes function to moderate cytopathogenicity by MV. These data advanced our understanding of molecular bases for MV pathogenicity and mechanisms of MV adaptation to grow in cultured cells.