INDIVIDUAL EXPRESSION OF INFLUENZA-VIRUS PA PROTEIN INDUCES DEGRADATION OF COEXPRESSED PROTEINS

In the process of in vivo reconstitution of influenza virus transcript ase-replicase complex, an inhibitory effect was observed when the leve l of PA protein expression was increased. This inhibition was parallel ed by a decrease in the accumulation of the other influenza virus core proteins. The sole expression of PA protein was sufficient to reduce the accumulation level of the proteins encoded by the coexpressed gene s. The PA effect was observed upon influenza virus and non-influenza v irus proteins and independently of the expression system chosen and th e origin of cell line used. The expression of PA protein did not induc e variations in the translation of the target proteins but did induce variations on their half-lives, which were clearly reduced. A function al PA subunit seems to be necessary to induce this negative effect, be cause an inactive point mutant was unable to decrease the steady-state levels or the half-lives of the reporter proteins. The PA effect was observed as early as 5 h after its expression, and continuous synthesi s of proteins was not required for performance of its biological activ ity. The results presented represent the first biological activity of individually expressed PA polymerase subunit.