Cold-adapted vaccine strains of influenza A virus act as dominant negative mutants in mixed infections with wild-type influenza A virus.
The cold-adapted reassortant of influenza A, which is a candidate live virus vaccine, interfered with the replication of parental wild-type virus in mixed infections of either MDCK cells or embryonated eggs. The interference occurred at either the permissive or nonpermissive temperature for the cold-adapted virus. In doubly infected cells, the yield of the wild-type virus was reduced by as much as 3000-fold and the protein synthesis phenotype expressed was that of the cold-adapted virus. The interference was detected even when infection with wild-type virus was carried out at a 9-fold excess or 2 hr before infection with the cold-adapted virus. As well as interfering with its wild-type parental virus, the cold-adapted virus also inhibited the replication of a heterologous influenza A subtype. In addition to its immunogenic potential, the ability to interfere with the replication of wild-type viruses is a desirable trait for any live, attenuated virus vaccine.
Whitaker-Dowling
P
P
Department of Microbiology, Biochemistry and Molecular Biology, School of Medicine, University of Pittsburgh, Pennsylvania 15261.
Lucas
W
W
Youngner
J S
JS
D000818:Animals; D002460:Cell Line; D002642:Chick Embryo; D003080:Cold Temperature; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007252:Influenza Vaccines; D009154:Mutation; D014613:Vaccines, Attenuated; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication
D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D014764:Viral Proteins