Journal article

Receptor specificity of the influenza virus hemagglutinin modulates sensitivity to soluble collectins of the innate immune system and virulence in mice

Michelle D Tate, Andrew G Brooks, Patrick C Reading

VIROLOGY | ACADEMIC PRESS INC ELSEVIER SCIENCE | Published : 2011

Abstract

The hemagglutinin (HA) glycoprotein of influenza virus binds to cell surface sialic acid (SA) to initiate infection. In this study, a mutant of influenza A virus strain BJx109 (H3N2) was plaque-purified from the lungs of virus-infected mice that had been depleted of airway macrophages. Sequence analysis identified a single amino acid substitution (S186I) in the vicinity of the receptor-binding site of HA. This substitution was associated with enhanced binding to α(2,3)-Gal-linked SA and an increased ability to infect murine airway epithelial cells. Mutant viruses were less sensitive to neutralization by mouse airway fluids and less efficient in their ability to infect murine macrophages. Mor..

View full abstract

Grants

Awarded by National Health and Medical Research Council (NH&MRC) of Australia


Funding Acknowledgements

This study was supported by Project Grant #509230 from The National Health and Medical Research Council (NH&MRC) of Australia. P.C.R. is a NH&MRC R.D. Wright Research Fellow. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health and Ageing. The authors wish to thank Dr. Robert Webster, St Jude Children's Research Hospital, Memphis, Tennessee, USA, for provision of the plasmid vector used to create the reverse engineered viruses for this study.