Journal article
Ferrets exclusively synthesize Neu5Ac and express naturally humanized influenza A virus receptors
PSK Ng, R Böhm, LE Hartley-Tassell, JA Steen, H Wang, SW Lukowski, PL Hawthorne, AEO Trezise, PJ Coloe, SM Grimmond, T Haselhorst, M Von Itzstein, AW Paton, JC Paton, MP Jennings
Nature Communications | Published : 2014
DOI: 10.1038/ncomms6750
Open access
Abstract
Mammals express the sialic acids N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) on cell surfaces, where they act as receptors for pathogens, including influenza A virus (IAV). Neu5Gc is synthesized from Neu5Ac by the enzyme cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH). In humans, this enzyme is inactive and only Neu5Ac is produced. Ferrets are susceptible to human-adapted IAV strains and have been the dominant animal model for IAV studies. Here we show that ferrets, like humans, do not synthesize Neu5Gc. Genomic analysis reveals an ancient, nine-exon deletion in the ferret CMAH gene that is shared by the Pinnipedia and Musteloidia members of the ..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
We thank Wang Guilin from the Yale Center for Genome Analysis and Matthew Boitano of Pacific Biosciences Sequencing for SMRT sequencing and analysis, BACPAC Resource Center (BPRC) at the Children's Hospital Oakland Research Institute in Oakland, California, for supplying BAC filters and Pieter de Jong of BPRC for assistance and technical advice, the WHO Collaborating Centre for Reference and Research on Influenza (VIDRL) for providing MDCK cells and IAV strains, the Australian Veterinary Services Division of SA Pathology (IMVS), South Australia, for provision of ferret tissues, Australian Proteome Analysis Facility (APAF) for providing sugar analysis service measuring sialic acids. Research was facilitated by access to the Australian Proteome Analysis Facility supported under the Australian Government's National Collaborative Research Infrastructure Strategy. This work was supported by Programme Grant 565526 from the National Health and Medical Research Council of Australia (NHMRC) (to A.W.P., J.C.P. and M.P.J.), NHMRC Project Grant 1006618 (to M.v.I.) and Australian Research Council (ARC) Discovery Grant DP120103178 (to A.W.P.) and DP130102945 (to M.v.I.). J.C.P. is a NHMRC Senior Principal Research Fellow; A.W.P. is an ARC DORA Fellow. Griffith University is gratefully acknowledged for the provision of scholarships to P.S.K.N. and R.B. We also thank Dr Sharon Birks and the Burke Museum of Natural History and Culture, University of Washington for assistance in providing animal tissue used in this study.