Ts mutant of NWS influenza virus: behaviour in vitro and in vivo

After passaging the NWS influenza virus at increasing temperatures in the hamster embryo fibroblast (HEF) cell line, a temperature-resistant (tr) mutant which grew well at 39 degrees C was isolated. Attempts were made to isolate temperature-sensitive (ts) mutants from the tr virus. After growth in the presence of 5-fluorouracil, 233 virus clones were isolated. Among these only one was incapable of replicating at 39 degrees C. The physiological studies, the shift-up experiment and the electron microscopic investigation suggested that the genetic defect responsible for its ts character influenced a late function of the virus genome. In the lungs of intranasally infected mice, the ts mutant replicated to a lesser extent than the tr virus. During its growth in vivo, the ts virus exhibited a high degree of genetic stability.