Dr. Alison Yao
The 1918 “Spanish flu” pandemic was caused by an H1N1 strain of influenza A virus (IAV) and killed 50 to 100 million people worldwide. The Wilson-Smith 1933 H1N1 strain is genetically similar to the 1918 pandemic influenza virus and was the first influenza virus cultured in the lab. Influenza A virus belongs to a viral class called negative-sense RNA viruses. In order for this type of virus to replicate, its RNA must first be converted to a complementary molecule: positive-sense RNA. This is accomplished by a group of proteins called the RNA-dependent RNA polymerase complex. Three proteins make up the complex: polymerase basic protein 1, polymerase basic protein 2, and polymerase acidic (PA) protein. This complex poses an attractive target for antiviral drug development.
The Seattle Structural Genomics Center for Infectious Disease has determined the first structure of the apo c-terminal domain of the PA protein from the 1933 Wilson-Smith IAV strain (A/WS/1933/H1N1 UniProt ID P15659). The structure shows the latter two-thirds of the protein (residues 254 through the native C-terminus at 716). It reveals the first view of a critical residue, S552. Mutation of S552 may allow avian influenza strains to bypass the species-species restriction of the avian polymerase complex and cross species to humans.