Laboratory characteristics of attenuated influenza viruses

Abstract

The selection of attenuated mutants of a virus related to A2/Tokyo/3/67 and of the subtype A2/Hong Kong/1/68 is described. By passing the former in the presence of heated horse serum it was possible to obtain a strain wholly resistant to thermostable horse-serum inhibitor. A2/Hong Kong/1/68 was, however, rendered only partially resistant by this technique. In subsequent volunteer trials it was clear that inhibitor-resistance was a marker of attenuation. Residual inhibitor-sensitivity was associated with some remaining pathogenicity. Inhibitor-resistant viruses were infective and antigenic.Inhibitor-sensitive viruses were also attenuated by repeated passage at 25 degrees C. When this was attempted with the partially inhibitor-resistant form of A2/Hong Kong/1/68, the virus became over-attenuated.In the laboratory, inhibitor-resistant viruses were shown to elute more rapidly from red blood cells than their inhibitor-sensitive parents and to grow better at 40 degrees C.