Polymorphism of the NS1 proteins of type A influenza virus.

The type-specific non-structural protein 1 (NS1) of influenza A viruses was found to be heterogeneous with respect to charge, varying in pI by more than two orders of magnitude, and to phosphorylation. Phosphorylation was strain-specific, variable in extent between strains, and in some strains NS1 proteins were not detectably phosphorylated. Phosphorylation was not responsible for the major variations in charge as, paradoxically, the most acidic NS1 proteins were not phosphorylated. Cytoplasmic inclusions, which are formed between NS1 proteins and cellular RNA in infections with a number of human strains, were absent from A/FP/Rostock-infected cells and do not, therefore, appear to be essential in virus multiplication. We suggest that the acidic nature of the NS1 of A/FP/Rostock may prevent it from binding RNA and hence from forming inclusions. The variation in charge of NS1 proteins which we determined experimentally correlates with the overall differences in charge adduced from published amino acid sequence and implications of this variability to the biological role of NS1 are discussed.