John McCauley

Crick Worldwide Influenza Centre

Influenza viruses infect a variety of species. Humans, horses and pigs are the main mammalian hosts of the virus in which infection is sustained. Avian species, particularly water fowl and gulls, harbour a very wide variety of influenza viruses. New pandemic strains of human influenza viruses arise from an animal reservoir either directly, as in the 2009 pandemic virus, or as a result of gene reassortment, as occurred in the 1957 and 1968 pandemics. The interaction between a virus particle and its receptor on a host cell is a vital feature that limits the host range of influenza viruses, but additional factors following entry of virus into the cell also control the outcome of infection.

In our laboratory, we are investigating the determinants of host range restriction of avian and swine influenza viruses that limit their ability to infect and propagate in human cells. We are also characterising the factors that influence the replication of avian influenza viruses in avian species. In collaboration with colleagues at The Institute for Animal Health, the Veterinary Laboratories Agency and the Wellcome Trust Sanger Institute we have been examining how the virus varies within the infected avian host. The techniques used have allowed us to analyse polymorphisms within the virus and the background genetic variation seen within samples amplified directly from experimentally infected birds.

Figure 1

Variants per read graph (Click to view larger image)

cDNA clones were prepared directly from samples taken from an experimentally infected chickens. The numbers of nucleotide changes (black bars) and amino acid changes (grey bars) in individual clones differing from the consensus sequence clone are indicated.

Selected publications

Iqbal, M; Xiao, H; Baillie, G; Warry, A; Essen, SC; Londt, B; Brookes, SM; Brown, IH and McCauley, JW (2009) Within-host variation of avian influenza viruses. Philosophical Transactions of the Royal Society B-Biological Sciences 364, 2739-2747

Iqbal, M; Yaqub, T; Reddy, K and McCauley, JW (2009) Novel genotypes of H9N2 influenza A viruses isolated from poultry in Pakistan containing NS genes similar to highly pathogenic H7N3 and H5N1 viruses. PLoS ONE 4, e5788

Kuiken, T; Holmes, EC; McCauley, J; Rimmelzwaan, GF; Williams, CS and Grenfell, BT (2006) Host species barriers to influenza virus infections. Science 312, 394-397

John McCauley
+44 (0)20 379 61520