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.