Decoding the Distribution of Glycan Receptors for Human-adapted Influenza A Viruses in Ferret Respiratory Tract

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Feb 24

PMID 22359533

Citations 48

Authors

Akila Jayaraman

Aarthi Chandrasekaran

Karthik Viswanathan

Rahul Raman

James G Fox

Ram Sasisekharan

Affiliations

Soon will be listed here.

Abstract

Ferrets are widely used as animal models for studying influenza A viral pathogenesis and transmissibility. Human-adapted influenza A viruses primarily target the upper respiratory tract in humans (infection of the lower respiratory tract is observed less frequently), while in ferrets, upon intranasal inoculation both upper and lower respiratory tract are targeted. Viral tropism is governed by distribution of complex sialylated glycan receptors in various cells/tissues of the host that are specifically recognized by influenza A virus hemagglutinin (HA), a glycoprotein on viral surface. It is generally known that upper respiratory tract of humans and ferrets predominantly express α2→6 sialylated glycan receptors. However much less is known about the fine structure of these glycan receptors and their distribution in different regions of the ferret respiratory tract. In this study, we characterize distribution of glycan receptors going beyond terminal sialic acid linkage in the cranial and caudal regions of the ferret trachea (upper respiratory tract) and lung hilar region (lower respiratory tract) by multiplexing use of various plant lectins and human-adapted HAs to stain these tissue sections. Our findings show that the sialylated glycan receptors recognized by human-adapted HAs are predominantly distributed in submucosal gland of lung hilar region as a part of O-linked glycans. Our study has implications in understanding influenza A viral pathogenesis in ferrets and also in employing ferrets as animal models for developing therapeutic strategies against influenza.

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References

Tumpey T, Maines T, Van Hoeven N, Glaser L, Solorzano A, Pappas C . A two-amino acid change in the hemagglutinin of the 1918 influenza virus abolishes transmission. Science. 2007; 315(5812):655-9. DOI: 10.1126/science.1136212. View

Watanabe T, Watanabe S, Shinya K, Kim J, Hatta M, Kawaoka Y . Viral RNA polymerase complex promotes optimal growth of 1918 virus in the lower respiratory tract of ferrets. Proc Natl Acad Sci U S A. 2008; 106(2):588-92. PMC: 2626747. DOI: 10.1073/pnas.0806959106. View

Garcia-Sastre A . Influenza virus receptor specificity: disease and transmission. Am J Pathol. 2010; 176(4):1584-5. PMC: 2843447. DOI: 10.2353/ajpath.2010.100066. View

Matrosovich M, Matrosovich T, Gray T, Roberts N, Klenk H . Human and avian influenza viruses target different cell types in cultures of human airway epithelium. Proc Natl Acad Sci U S A. 2004; 101(13):4620-4. PMC: 384796. DOI: 10.1073/pnas.0308001101. View

Perini J, Aubert J, Porchet N, Mazzuca M, Lamblin G, HERSCOVICS A . Multiple apomucin translation products from human respiratory mucosa mRNA. Eur J Biochem. 1991; 196(2):321-8. DOI: 10.1111/j.1432-1033.1991.tb15820.x. View

Maines T, Chen L, Matsuoka Y, Chen H, Rowe T, Ortin J . Lack of transmission of H5N1 avian-human reassortant influenza viruses in a ferret model. Proc Natl Acad Sci U S A. 2006; 103(32):12121-6. PMC: 1567706. DOI: 10.1073/pnas.0605134103. View

Triana-Baltzer G, Babizki M, Chan M, Wong A, Aschenbrenner L, Campbell E . DAS181, a sialidase fusion protein, protects human airway epithelium against influenza virus infection: an in vitro pharmacodynamic analysis. J Antimicrob Chemother. 2009; 65(2):275-84. PMC: 2809246. DOI: 10.1093/jac/dkp421. View

Rogers D . Airway goblet cells: responsive and adaptable front-line defenders. Eur Respir J. 1994; 7(9):1690-706. View

Maines T, Jayaraman A, Belser J, Wadford D, Pappas C, Zeng H . Transmission and pathogenesis of swine-origin 2009 A(H1N1) influenza viruses in ferrets and mice. Science. 2009; 325(5939):484-7. PMC: 2953552. DOI: 10.1126/science.1177238. View

10.

Leigh M, Connor R, Kelm S, Baum L, Paulson J . Receptor specificity of influenza virus influences severity of illness in ferrets. Vaccine. 1995; 13(15):1468-73. DOI: 10.1016/0264-410x(95)00004-k. View

11.

van Riel D, Munster V, de Wit E, Rimmelzwaan G, Fouchier R, Osterhaus A . Human and avian influenza viruses target different cells in the lower respiratory tract of humans and other mammals. Am J Pathol. 2007; 171(4):1215-23. PMC: 1988871. DOI: 10.2353/ajpath.2007.070248. View

12.

Viswanathan K, Chandrasekaran A, Srinivasan A, Raman R, Sasisekharan V, Sasisekharan R . Glycans as receptors for influenza pathogenesis. Glycoconj J. 2010; 27(6):561-70. PMC: 3407351. DOI: 10.1007/s10719-010-9303-4. View

13.

van Riel D, den Bakker M, Leijten L, Chutinimitkul S, Munster V, de Wit E . Seasonal and pandemic human influenza viruses attach better to human upper respiratory tract epithelium than avian influenza viruses. Am J Pathol. 2010; 176(4):1614-8. PMC: 2843453. DOI: 10.2353/ajpath.2010.090949. View

14.

Husseini R, Sweet C, Bird R, Collie M, Smith H . Distribution of viral antigen with the lower respiratory tract of ferrets infected with a virulent influenza virus: production and release of virus from corresponding organ cultures. J Gen Virol. 1983; 64 Pt 3:589-98. DOI: 10.1099/0022-1317-64-3-589. View

15.

Srinivasan A, Viswanathan K, Raman R, Chandrasekaran A, Raguram S, Tumpey T . Quantitative biochemical rationale for differences in transmissibility of 1918 pandemic influenza A viruses. Proc Natl Acad Sci U S A. 2008; 105(8):2800-5. PMC: 2268540. DOI: 10.1073/pnas.0711963105. View

16.

Stevens J, Blixt O, Paulson J, Wilson I . Glycan microarray technologies: tools to survey host specificity of influenza viruses. Nat Rev Microbiol. 2006; 4(11):857-64. PMC: 7097745. DOI: 10.1038/nrmicro1530. View

17.

van Riel D, Munster V, de Wit E, Rimmelzwaan G, Fouchier R, Osterhaus A . H5N1 Virus Attachment to Lower Respiratory Tract. Science. 2006; 312(5772):399. DOI: 10.1126/science.1125548. View

18.

Gambaryan A, Piskarev V, Yamskov I, SAKHAROV A, Tuzikov A, Bovin N . Human influenza virus recognition of sialyloligosaccharides. FEBS Lett. 1995; 366(1):57-60. DOI: 10.1016/0014-5793(95)00488-u. View

19.

Mansfield K . Viral tropism and the pathogenesis of influenza in the Mammalian host. Am J Pathol. 2007; 171(4):1089-92. PMC: 1988860. DOI: 10.2353/ajpath.2007.070695. View

20.

Kirkeby S, Martel C, Aasted B . Infection with human H1N1 influenza virus affects the expression of sialic acids of metaplastic mucous cells in the ferret airways. Virus Res. 2009; 144(1-2):225-32. DOI: 10.1016/j.virusres.2009.05.004. View