Influenza virus replication at the molecular level
Influenza viruses are important human and animal pathogens. They cause widespread clinical and veterinary disease and have a considerable economic impact. Our laboratory seeks to understand fundamental aspects of the structure and function of influenza viruses, as well as virus:host interactions including host responses to viral infection; such studies are required for the development of novel strategies to combat influenza.
Our main focus is the transcriptional machinery of influenza virus, a ribonucleoprotein complex consisting of viral RNA, a trimeric RNA-dependent RNA polymerase (made up of the subunits PA, PB1 and PB2), and a scaffold of nucleoprotein (NP). Our work addresses how the RNA polymerase replicates the viral RNA genome, via a complementary RNA (cRNA) replicative intermediate, and how it transcribes viral genes into mRNA. The RNA polymerase is a major determinant of the virulence and host range of influenza viruses, and is a key regulator of the adaptation of avian influenza viruses to mammalian hosts. We aim to understand the molecular mechanisms behind these activities by studying the cellular context of viral RNA polymerase function and the role of cellular proteins involved. We also study the subcellular localisation of viral proteins during infection and their regulation by post-translational modification, and the contribution of host proteins to influenza virion architecture.
To address these fundamental questions we collaborate with structural biologists, physicists, chemists and immunologists using an inter-disciplinary approach with cutting-edge technologies including molecular and cell biology, proteomics, single molecule and super-resolution microscopy, structural biology, and virology.
Nat Rev Microbiol 14: 479 - 493.
Nature 527: 114-117.
Nature Commun 5: 4816.
Proc Natl Acad Sci U S A 110: 4238-4245.
Nature 458: 909-913.