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The neuraminidase activity of influenza A virus determines the strain-specific sensitivity to neutralization by respiratory mucus


Iseli, Alena N; Pohl, Marie O; Glas, Irina; Gaggioli, Elisabeth; Martínez-Barragán, Patricia; David, Shannon C; Schaub, Aline; Luo, Beiping; Klein, Liviana K; Bluvshtein, Nir; Violaki, Kalliopi; Motos, Ghislain; Hugentobler, Walter; Nenes, Athanasios; Krieger, Ulrich K; Peter, Thomas; Kohn, Tamar; Stertz, Silke (2023). The neuraminidase activity of influenza A virus determines the strain-specific sensitivity to neutralization by respiratory mucus. Journal of Virology, 97(10):e0127123.

Abstract

The respiratory tract of humans is constantly exposed to potentially harmful agents, such as small particles or pathogens, and thus requires protective measures. Respiratory mucus that lines the airway epithelia plays a major role in the prevention of viral infections by limiting the mobility of viruses, allowing subsequent mucociliary clearance. Understanding the interplay between respiratory mucus and viruses can help elucidate host and virus characteristics that enable the initiation of infection. Here, we tested a panel of primary influenza A viruses of avian or human origin for their sensitivity to mucus derived from primary human airway cultures and found that differences between virus strains can be mapped to viral neuraminidase activity. We also show that binding of influenza A viruses to decoy receptors on highly glycosylated mucus components constitutes the major inhibitory function of mucus against influenza A viruses.

Abstract

The respiratory tract of humans is constantly exposed to potentially harmful agents, such as small particles or pathogens, and thus requires protective measures. Respiratory mucus that lines the airway epithelia plays a major role in the prevention of viral infections by limiting the mobility of viruses, allowing subsequent mucociliary clearance. Understanding the interplay between respiratory mucus and viruses can help elucidate host and virus characteristics that enable the initiation of infection. Here, we tested a panel of primary influenza A viruses of avian or human origin for their sensitivity to mucus derived from primary human airway cultures and found that differences between virus strains can be mapped to viral neuraminidase activity. We also show that binding of influenza A viruses to decoy receptors on highly glycosylated mucus components constitutes the major inhibitory function of mucus against influenza A viruses.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Virology
Dewey Decimal Classification:610 Medicine & health
570 Life sciences; biology
Scopus Subject Areas:Life Sciences > Microbiology
Life Sciences > Immunology
Life Sciences > Insect Science
Life Sciences > Virology
Uncontrolled Keywords:influenza; mucus; neutralization
Language:English
Date:31 October 2023
Deposited On:15 Jan 2024 14:26
Last Modified:30 Jun 2024 01:37
Publisher:American Society for Microbiology
ISSN:0022-538X
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1128/jvi.01271-23
PubMed ID:37819131
  • Content: Published Version
  • Language: English