Selective translation of
influenza viral mRNAs occurs after influenza virus
superinfection of cells infected with the
VAI RNA-negative adenovirus mutant dl331 (M. G. Katze, Y.-T. Chen, and R. M. Krug, Cell 37:483-490, 1984).
Cell extracts from these doubly infected cells catalyze the initiation of essentially only
influenza viral protein synthesis, reproducing the in vivo situation. This selective translation is correlated with a 5- to 10-fold suppression of the dl331-induced
kinase that phosphorylates the alpha subunit of eucaryotic
initiation factor eIF-2. This strongly suggests that influenza virus encodes a gene product that, analogous to the adenoviral
VAI RNA, prevents the shutdown of overall
protein synthesis caused by an
eIF-2 alpha kinase turned on by
viral infection. Adenoviral mRNA translation was restored to the extract from the doubly infected cells by the addition of the
guanine nucleotide exchange factor eIF-2B, which is responsible for the normal recycling of
eIF-2 during
protein synthesis. This indicates that the residual
kinase in the doubly infected cells leads to a limitation in functional (nonsequestered)
eIF-2B and hence functional (
GTP-containing)
eIF-2 and that under these conditions
influenza viral mRNAs are selectively translated over adenoviral mRNAs. Addition of
double-stranded RNA to the extracts from these cells restored the
eIF-2 alpha kinase to a level approaching that seen in extracts from cells infected with dl331 alone and caused the inhibition of
influenza viral mRNA translation. This suggests that the putative
influenza viral gene product acts against the
double-stranded RNA activation of the
kinase and indicates that
influenza viral mRNA translation is also linked to the level of functional
eIF-2. Our results thus indicate that a limitation in functional
eIF-2 which causes a nonspecific reduction in the rate of initiation of
protein synthesis results in the preferential translation of the better mRNAs (
influenza viral mRNAs) at the expense of the poorer mRNAs (adenoviral mRNAs).