Abstract: The influenza A/Alaska/77-ts-1A2 vaccine candidate strain, which has a 37° shutoff temperature for plaque formation and temperature-sensitive (ts) lesions on the P1 and P3 genes, was administered intranasally to a seronegative child who subsequently remained well. However, starting 7 days after inoculation, A/Alaska/77 virus with a 40° shutoff temperature (ts+) was shed. To determine whether an extragenic suppressor mutation was responsible for this loss of ts phenotype of the vaccine candidate virus, the ts+ isolate was mated with wild-type virus, and ts recombinant progeny were sought. Approximately 25% of the progeny were ts, suggesting that a suppressor mutation was present in the child's ts+ isolate. Each of 62 ts progeny viruses had the ts P3 gene. The extragenic suppressor of this ts gene was localized to the P2 gene. The ts P3 gene of the A/Alaska/77-ts-1A2 recombinant specified a 37–38° shutoff temperature for plaque formation, whereas the ts P3 gene in the ts segregants derived from the ts+ isolate had a 39° shutoff temperature. Hence, the ts P3 gene in the ts+ isolate developed an intragenic mutation affecting its level of temperature sensitivity. In addition, the P3 RNA of the ts+ virus migrated more slowly in polyacrylamide gel than the P3 RNA of its A/Alaska/77-ts-1A2 parent. We failed to isolate ts P1 segregants from the ts+ isolate, indicating that the P1 ts mutation had reverted or undergone intragenic suppression. The ability of ts mutants to escape from their ts phenotype by suppression and other mutations may limit their usefulness in immunoprophylaxis since attenuation of ts mutants of influenza virus appears to be a function of the ts phenotype. Additionally, suppressor mutations provide new opportunities for studying the nature of protein-protein interactions.

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{{Explor lien
   |wiki=    Sante
   |area=    H2N2V1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     ISTEX:F8B30400DE92CE68D6CB321902227B108E7C2901
   |texte=   Genetic factors associated with loss of the temperature-sensitive phenotype of the influenza A/Alaska/77-ts-1A2 recombinant during growth in vivo
}}