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Temperature-Sensitive Mutants of Influenza A Virus: Production and Characterization of A/Victoria/3/75- ts -1[E] Recombinants

1978; American Society for Microbiology; Volume: 20; Issue: 3 Linguagem: Inglês

10.1128/iai.20.3.665-670.1978

1098-5522

Brian R. Murphy, Nanette T. Hosier, Susan B. Spring, Steven R. Mostow, Robert M. Chanock,

Virus-based gene therapy research

The Hong Kong/68- ts -1[E] virus, which has a 38°C shutoff temperature for plaque formation, has been proposed as a donor of its two ts lesions to new variants of influenza A virus that pose an epidemic threat. To further examine whether the acquisition of the two ts -1[E] lesions will predictably attenuate new influenza A variants, the HK/68- ts -1[E] virus was mated with the A/Vic/3/75 wild-type virus. The Vic/75- ts -[E] recombinants that had the two ts -1[E] lesions also had a 38°C shutoff temperature. Two Vic/75- ts -1[E] recombinants (clones 81 and 113) that had the two ts -1[E] lesions, a 38°C shutoff temperature, and the Vic/75 hemagglutinin and neuraminidase glycoproteins were similar to each other and to their ts -1[E] parent in the pattern of replication and genetic stability in hamsters. These findings support the hypothesis that the acquisition of the two ts -1[E] lesions will predictably attenuate wild-type influenza A virus. Each Vic/75- ts -1[E] recombinant virus that possessed only the group 1 ts -1[E] lesion had a 39°C shutoff temperature. Two of three of the Vic/75- ts -1[E] recombinants that had only the group 2 ts -1[E] lesion had a 39°C shutoff temperature. This suggests that the HK/68- ts -1[E] donor virus contains two ts genes each of which by itself restricts plaque formation at 39°C and above. The HK/68- ts -1[E] parent virus and its Vic/75 recombinant clones 81 and 113 were evaluated in ferret tracheal organ cultures maintained at permissive and restrictive temperatures. The Vic/75- ts -1[E] clone 81 differed from its parent and sister clone 113 in that it replicated readily and caused ciliostasis at 37°C, a temperature restrictive for the replication of other ts -1[E] recombinants with a 38°C shutoff temperature. The genetic basis underlying this difference was not elucidated.