Interferon-gamma Inhibits Influenza A Virus Cellular Attachment by Reducing Sialic Acid Cluster Size

Overview

Journal iScience

Publisher Cell Press

Date 2022 Mar 25

PMID 35330686

Authors

Carol Ho-Yan Fong

Lu Lu

Lin-Lei Chen

Man-Lung Yeung

Anna Jinxia Zhang

Hanjun Zhao

Kwok-Yung Yuen

Kelvin Kai-Wang To

Affiliations

Soon will be listed here.

Abstract

The mucosal antiviral role of type I and III interferon in influenza virus infection is well established. However, much less is known about the antiviral mechanism of type II interferon (interferon-gamma). Here, we revealed an antiviral mechanism of interferon-gamma by inhibiting influenza A virus (IAV) attachment. By direct stochastic optical reconstruction microscopy, confocal microscopy, and flow cytometry, we have shown that interferon-gamma reduced the size of α-2,3 and α-2,6-linked sialic acid clusters, without changing the sialic acid or epidermal growth factor receptor expression levels, or the sialic acid density within cluster on the cell surface of A549 cells. Reversing the effect of interferon-gamma on sialic acid clustering by jasplakinolide reverted the cluster size, improved IAV attachment and replication. Our findings showed the importance of sialic acid clustering in IAV attachment and infection. We also demonstrated the interference of sialic acid clustering as an anti-IAV mechanism of IFN-gamma for IAV infection.

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References

Sauter N, Hanson J, Glick G, Brown J, Crowther R, Park S . Binding of influenza virus hemagglutinin to analogs of its cell-surface receptor, sialic acid: analysis by proton nuclear magnetic resonance spectroscopy and X-ray crystallography. Biochemistry. 1992; 31(40):9609-21. DOI: 10.1021/bi00155a013. View

Zhou Q, Chi X, Lee M, Hsieh W, Mkrtchyan J, Feng A . Interferon-mediated reprogramming of membrane cholesterol to evade bacterial toxins. Nat Immunol. 2020; 21(7):746-755. PMC: 7778040. DOI: 10.1038/s41590-020-0695-4. View

Chu H, Hu B, Huang X, Chai Y, Zhou D, Wang Y . Host and viral determinants for efficient SARS-CoV-2 infection of the human lung. Nat Commun. 2021; 12(1):134. PMC: 7794309. DOI: 10.1038/s41467-020-20457-w. View

Chen X, Liu S, Goraya M, Maarouf M, Huang S, Chen J . Host Immune Response to Influenza A Virus Infection. Front Immunol. 2018; 9:320. PMC: 5845129. DOI: 10.3389/fimmu.2018.00320. View

Feeley E, Sims J, John S, Chin C, Pertel T, Chen L . IFITM3 inhibits influenza A virus infection by preventing cytosolic entry. PLoS Pathog. 2011; 7(10):e1002337. PMC: 3203188. DOI: 10.1371/journal.ppat.1002337. View

Vanderheiden A, Ralfs P, Chirkova T, Upadhyay A, Zimmerman M, Bedoya S . Type I and Type III Interferons Restrict SARS-CoV-2 Infection of Human Airway Epithelial Cultures. J Virol. 2020; 94(19). PMC: 7495371. DOI: 10.1128/JVI.00985-20. View

Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T . Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012; 9(7):676-82. PMC: 3855844. DOI: 10.1038/nmeth.2019. View

Zhou J, Li C, Sachs N, Chiu M, Wong B, Chu H . Differentiated human airway organoids to assess infectivity of emerging influenza virus. Proc Natl Acad Sci U S A. 2018; 115(26):6822-6827. PMC: 6042130. DOI: 10.1073/pnas.1806308115. View

Doherty P, Turner S, Webby R, Thomas P . Influenza and the challenge for immunology. Nat Immunol. 2006; 7(5):449-55. DOI: 10.1038/ni1343. View

10.

To K, Mok K, Chan A, Cheung N, Wang P, Lui Y . Mycophenolic acid, an immunomodulator, has potent and broad-spectrum in vitro antiviral activity against pandemic, seasonal and avian influenza viruses affecting humans. J Gen Virol. 2016; 97(8):1807-1817. DOI: 10.1099/jgv.0.000512. View

11.

Wei X, Jia Z, Lian J, Zhang Y, Li J, Ma L . Inhibition of hepatitis C virus infection by interferon-gamma through downregulating claudin-1. J Interferon Cytokine Res. 2009; 29(3):171-8. DOI: 10.1089/jir.2008.0040. View

12.

Iwasaki A, Foxman E, Molony R . Early local immune defences in the respiratory tract. Nat Rev Immunol. 2016; 17(1):7-20. PMC: 5480291. DOI: 10.1038/nri.2016.117. View

13.

Chan C, Chu H, Zhang A, Leung L, Sze K, Kao R . Hemagglutinin of influenza A virus binds specifically to cell surface nucleolin and plays a role in virus internalization. Virology. 2016; 494:78-88. DOI: 10.1016/j.virol.2016.04.008. View

14.

Weiss I, Wald O, Wald H, Beider K, Abraham M, Galun E . IFN-gamma treatment at early stages of influenza virus infection protects mice from death in a NK cell-dependent manner. J Interferon Cytokine Res. 2010; 30(6):439-49. DOI: 10.1089/jir.2009.0084. View

15.

Goley E, Welch M . The ARP2/3 complex: an actin nucleator comes of age. Nat Rev Mol Cell Biol. 2006; 7(10):713-26. DOI: 10.1038/nrm2026. View

16.

Paul G, Marchelletta R, McCole D, Barrett K . Interferon-γ alters downstream signaling originating from epidermal growth factor receptor in intestinal epithelial cells: functional consequences for ion transport. J Biol Chem. 2011; 287(3):2144-55. PMC: 3265893. DOI: 10.1074/jbc.M111.318139. View

17.

Sieben C, Sezgin E, Eggeling C, Manley S . Influenza A viruses use multivalent sialic acid clusters for cell binding and receptor activation. PLoS Pathog. 2020; 16(7):e1008656. PMC: 7371231. DOI: 10.1371/journal.ppat.1008656. View

18.

Dhawan S, Heredia A, Wahl L, Epstein J, Meltzer M, Hewlett I . Interferon-gamma-induced downregulation of CD4 inhibits the entry of human immunodeficiency virus type-1 in primary monocytes. Pathobiology. 1995; 63(2):93-9. DOI: 10.1159/000163939. View

19.

Reading P, Miller J, Anders E . Involvement of the mannose receptor in infection of macrophages by influenza virus. J Virol. 2000; 74(11):5190-7. PMC: 110872. DOI: 10.1128/jvi.74.11.5190-5197.2000. View

20.

To K, Zhou J, Chan J, Yuen K . Host genes and influenza pathogenesis in humans: an emerging paradigm. Curr Opin Virol. 2015; 14:7-15. PMC: 7102748. DOI: 10.1016/j.coviro.2015.04.010. View