Evaluation of a phenotypic revertant of the A/Alaska/77-ts-1A2 reassortant virus in hamsters and in seronegative adult volunteers: Further evidence that the temperature-sensitive phenotype is responsible for attenuation of ts-1A2 reassortant viruses

Mark D. Tolpin, Mary Lou Clements, Myron M. Levine, Robert E. Black, Alfred J. Saah, William C. Anthony, Louis Cisneros, Robert M. Chanock, Brian R. Murphy

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

In a previous study, a seronegative child to whom attenuated A/Alaska/77-ts1A2 virus was administered (37°C shutoff temperature for plaque formation) shed virus with an altered temperature-sensitive (ts) phenotype (40°C shutoff temperature) (Murphy et al., Ann. N.Y. Acad. Sci. 354:172-182, 1980; Tolpin et al., Virology 112:505-517, 1981). This ts+ virus (FV1319) was evaluated for its level of replication in hamsters and for its virulence for humans. In hamsters, FV1319 ts+ virus replicated to the same level in the nasal turbinates as that to which the A/Alaska/77 wild-type virus replicated, but its replication in the lungs was reduced 40-fold. In contrast, the A/Alaska/77-ts-1A2 reassortant achieved a titer in hamster nasal turbinates that was significantly lower (P < 0.005) than those achieved by the wild-type and the FV1319 viruses; the A/Alaska/77-ts-1A2 reassortant was not recoverable from the lungs. In seronegative adult volunteers, the pattern of replication of the FV1319 virus was similar to that of the A/Aaska/77 wild-type virus. The illness induced by the FV1319 ts+ virus was also similar to that caused by the wild-type virus. In contrast, the A/Alaska/77-ts-1A2 reassortant was satisfactorily attenuated in adult volunteers. These results suggest that attenuation of the A/Alaska/77-ts-1A2 reassortant virus in humans is a function of the ts phenotype: loss of this phenotype restored virulence. The ability of the A/Alaska/77-ts-1A2 reassortant to lose its ts phenotype and regain virulence during growth in a permissive host limits the usefulness of the ts-1A2 reassortants as vaccine viruses for humans.

Original languageEnglish (US)
Pages (from-to)645-650
Number of pages6
JournalUnknown Journal
Volume36
Issue number2
DOIs
StatePublished - 1982
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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