A temperature-sensitive mutation in the acidic polymerase gene of an influenza A virus alters the regulation of viral protein synthesis

Abstract

The temperature-sensitive defect of mutant ts 263 of fowl plague virus (FPV) is located in the acidic polymerase (PA) gene and is due to a single base substitution (C2036T), which leads to an amino acid replacement (Ala671 to Val) in a highly conserved region of the protein. During passage at 33 degrees C ts 263 stably carries over a ninth RNA segment, which consists of a truncated PA gene. Although the deletion is in-frame and it is transcribed into mRNA, no corresponding protein is detected in vivo. After reversion to wild-type this extra RNA segment is immediately lost. At the non-permissive temperature of 40 degrees C no significant viral products of ts 263 are synthesized. Under semi-permissive conditions there is a relative, but very significant over-production of the M1 protein, which is not accompanied by a corresponding elevated M1 mRNA synthesis. These results are in agreement with the idea that the PA protein is involved in the regulation of viral protein synthesis at the level of expression of mRNA. Preinfection of chicken embryo cells with ts 263 at a semi-permissive temperature interferes with the replication of FPV wild-type indicating that premature availability of M1 might be detrimental for influenza virus replication.