Amino acid replacements leading to temperature-sensitive defects of the NS1 protein of influenza A virus.

The nonstructural (NS) genes of two influenza virus temperature-sensitive (ts) reassortants have been sequenced and compared with the corresponding wild type sequences. Ts 412 has a single base substitution (G100-->A) leading to an amino acid replacement (Arg 25-->Lys) in the NS1 protein. Ts 451 also has a single base substitution (U273-->C) leading to an amino acid replacement (Ser 83-->Pro) in the NS1 protein. In ts 412 infected cells at the nonpermissive temperature very little M1 and HA mRNA and proteins are synthesized, suggesting that NS1 is involved in a transcriptional regulation process. The ts mutation in ts 451 could be extragenically suppressed by replacement of the PB1 and/or PA protein genes of the mutant by the allelic genes of PR8. Both observations suggest that NS1 cooperates with the polymerase complex.