Cis-acting signals and trans-acting factors involved in influenza virus RNA synthesis

Influenza A virus RNA replication and expression is directed from cis-acting sequences present on the viral RNAs with the help of trans-acting factors encoded by the virus. Ribonucleoprotein (RNP) complexes reconstituted from synthetic cDNA-derived RNA and purified viral proteins have facilitated the dissection of these cis-acting signals and trans-acting factors. Prior to these studies influenza viruses and other negative-strand RNA viruses were refractory to molecular genetic manipulations. These reverse genetic studies have helped in defining the promoter and polyadenylation signals required for viral RNA synthesis. Studies involving the use of reconstituted RNP complexes have revealed that the viral proteins PB1, PB2, PA, and the nucleoprotein (NP) are necessary for replication and expression of influenza virus RNA. Inroads have also been made in determining the cellular proteins that participate in influenza virus gene expression and replication. The yeast interactive trap system has been used to identify and clone a gene (NPI-1), which encodes a protein that interacts with the influenza virus NP suggesting that this cellular protein is a trans-acting factor functioning in viral RNA synthesis.