Role of surface glycoproteins in influenza virus pyrogenicity

Eleven H3N2, seven H1N1 and three H3N1 influenza virus reassortants of the pyrogenic A/Puerto Rico/8/34-A/England/939/69 clone 7a (H3N2) (A/7A) and poorly pyrogenic A/Fiji/15899/83 (H1N1) (A/Fiji) parents were analysed genetically for the parental origin of their genes and for their pyrogenicity in ferrets. All H3N2 reassortants were pyrogenic and produced significantly more fever than A/Fiji but differences in pyrogenicity between them could not be correlated with either single or constellations of genes. All H1N1 reassortants were poorly pyrogenic compared with A/7A but one (Am29) produced significantly more fever than A/Fiji. No correlation of the increased fever with inserted A/7A genes was evident in Am29 and, while mutations were detected in the H1 haemagglutinin of this reassortant using monoclonal antibodies, similar mutations were present in the other H1N1 reassortants which showed no increase in fever production. The three H3N1 reassortants were intermediate in their pyrogenicity, being more pyrogenic than A/Fiji and less pyrogenic than A/7A. Overall, these results support previous conclusions that the haemagglutinin and/or neuraminidase play a major role in the pyrogenicity of influenza virus.