Influenza virus receptors in the human airway
Abstract
Although more than 100 people have been infected by H5N1 influenza A viruses, human-to-human transmission is rare. What are the molecular barriers limiting human-to-human transmission? Here we demonstrate an anatomical difference in the distribution in the human airway of the different binding molecules preferred by the avian and human influenza viruses. The respective molecules are sialic acid linked to galactose by an alpha-2,3 linkage (SAalpha2,3Gal) and by an alpha-2,6 linkage (SAalpha2,6Gal). Our findings may provide a rational explanation for why H5N1 viruses at present rarely infect and spread between humans although they can replicate efficiently in the lungs.
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Seasonal influenza A virus binds to α2-6 sialylated glycans on cells in the upper respiratory tract, whereas highly pathogenic avian H5N1 binds to α2-3 sialylated glycans on type 2 pneumocytes lining lung alveoli.
“traditionally seasonal influenza A virus binds to α2-6 sialylated glycans on cells in the upper respiratory tract whereas the highly pathogenic avian H5N1 strain binds to α2-3 sialylated glycans on type 2 pneumocytes lining lung alveoli (Shinya et al., 2006).”
From Secondary bacterial infections associated with influenza pandemics (2017) · cites this paper as Shinya et al., 2006
In severe infections affecting the deep tissues of the respiratory tract, it is probable that the immunological cascade that takes place directly in the deep tissues is crucial to immunopathology rather than what can be measured as a 'spillover' in the peripheral blood.
“For instance, in severe infections affecting the deep tissues of the respiratory tract (as has been described in avian influenza or severe primary influenza virus infections), it is probable that it is the immunological cascade that takes place directly in the deep tissues that is crucial to immunopathology rather than what can be measured as a “spillover” in the peripheral blood (28,82,128).”
From Into the Eye of the Cytokine Storm (2012) · cites this paper as [128]
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- Authors
- Shinya, K., Ebina, M., Yamada, S., Ono, M., Kasai, N., & Kawaoka, Y.
- Affiliations
- University of Wisconsin–Madison (US)
- Tohoku University (JP)
- The University of Tokyo (JP)
- Corresponding author
- Kawaoka, Yoshihiro
- Venue
- Nature
- Published
- 2006-03
- Volume
- 440
- Issue
- 7083
- Pages
- 435-436
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2072237100
- Cited by
- 1,398
- References
- 8
- Citations by year
- 2026: 35 · 2025: 56 · 2024: 47 · 2023: 46 · 2022: 45 · 2021: 56 · 2020: 56 · 2019: 54 · 2018: 52 · 2017: 46 · 2016: 57 · 2015: 64 · 2014: 86 · 2013: 98 · 2012: 88
- FWCI
- 76.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- influenza virus receptor, H5N1 avian influenza, human-to-human transmission, sialic acid, human airways, upper and lower respiratory tract, viral tropism, respiratory anatomy
- MeSH terms
- Animals, Birds, Bronchi, Galactose, Humans, Influenza A virus, Pulmonary Alveoli, Receptors, Virus, Species Specificity, N-Acetylneuraminic Acid, Respiratory Mucosa, Influenza A Virus, H5N1 Subtype
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