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Evaluation of five temperature‐sensitive mutants of respiratory syncytial virus in primates: II. Genetic analysis of virus recovered during infection
Author(s) -
Belshe Robert B.,
Richardson Linda S.,
London William T.,
Sly D. Lewis,
Camargo Ena,
Prevar David A.,
Chanock Robert M.
Publication year - 1978
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.1890030203
Subject(s) - virus , virulence , biology , virology , mutant , infectivity , gene , genetics
Five temperature‐sensitive ( ts ) mutants of respiratory syncytial (RS) virus ( ts ‐1, ts ‐1, NG‐1, ts ‐1, NG‐16, ts ‐2, and ts ‐7), previously evaluated for infectivity and virulence in chimpanzees and owl monkeys, were also assayed for in vivo genetic stability. None of the five mutants tested was completely stable genetically. Thus, virus which had lost some or all of the ts property was recovered from each infected chimpanzee. Significantly, each ts ‐1 NG‐1 isolate retained some degree of temperature sensitivity and hence was not true wild‐type virus. Clonal analysis of viruses shed by ts ‐1, ts ‐1, NG‐1, ts ‐1, NG‐16, or ts ‐7 infected chimpanzees indicated that in most instances only a minority of the virus shed was altered genetically. Of five chimpanzees infected with the ts ‐2 mutant, three shed only ts virus, and the remaining two chimpanzees shed only ts + virus. Such ts + virus proved to be avirulent when evaluated in chimpanzees or owl monkeys, indicating that loss of the ts property did not restore virulence. Based upon these findings, the ts ‐2 mutant appears to be a suitable candidate for clinical trials in man.

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