First structures of the genome replication machinery of influenza A virus

First structures of the genome replication machinery of influenza A virus

Influenza A viruses are the most common cause of seasonal flu in humans and also infect animals, representing significant public health and economic burdens. During infection, the virus invades host cells and makes many copies of its RNA genome to produce new virus particles. RNA-dependent RNA polymerase is the enzyme responsible for this genome replication.

A collaboration between the Fodor group and the group of Jonathan Grimes (Division of Structural Biology, University of Oxford) published in Nature has revealed how influenza A virus RNA polymerase replicates the genome. Using cryo-electron microscopy and X-ray crystallography, they have produced the first high-resolution structures of human and avian influenza A virus RNA polymerases. Their results show that the influenza A virus RNA polymerase forms a dimeric complex, where one of the polymerases activates the other to copy RNA. However, if dimerisation is blocked viral genome replication is inhibited, meaning the virus cannot propagate. Therefore, the dimerisation interface is an attractive target for antiviral drug development, made possible by these first structures.

 

Isabella Maudlin

Fan H, Walker AP, Carrique L, Keown JR, Serna Martin I, Karia D, Sharps J, Hengrung N, Pardon E, Steyaert J, Grimes JM, Fodor E (2019).