Amantadine-resistant and -sensitive influenza A strains and recombinants

Several influenza A strains and recombinants of fowl plague virus (FPV) with a known gene constellation were tested for amantadine sensitivity under two different experimental conditions. In a haemagglutinin yield analysis of a single growth cycle experiment FPV was found to be highly sensitive to amantadine, while in the plaque reduction and inhibition test it was highly resistant. With the A3 Hong Kong and equi 2 strains the opposite observation was made. The A2 Singapore strain was sensitive while Ao PR8 was resistant in both tests. In the haemagglutinin yield analysis of a single growth cycle all recombinants carrying segment 4 (HA) of the resistant strain were resistent against amantadine, independent of the derivation of the other genes. In the plaque reduction and inhibition test recombinants carrying the haemagglutinin of the sensitive strain were either resistant or sensitive depending on the gene constellation. Drug sensitivity was transferred by the combination of segments 5 (NP) and 6 (NA). Segment 7 (M) of certain sensitive strains seems to counteract this effect. The results are compatible with the concept that amantadine resistance or sensitivity is not confined to a single gene product or a single mechanism.