Avian flu: Influenza virus receptors in the human airway

  title={Avian flu: Influenza virus receptors in the human airway},
  author={Kyoko Shinya and Masahito Ebina and Shinya Yamada and Masao Ono and Noriyuki Kasai and Yoshihiro Kawaoka},
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 α-2,3 linkage (SAα2,3Gal) and by an α-2,6 linkage (SAα2,6Gal). Our findings… 
[Influenza virus receptors in the human airway].
It is demonstrated that the epithelial cells in the upper respiratory tract of humans mainly possess sialic acid linked to galactose by alpha 2,6 linkages, a molecule preferentially recognized by human viruses, which is consistent with the observation that H5N1 viruses can be directly transmitted from birds to humans and cause serious lower respiratory tract damage in humans.
Avian influenza A(H5N1) viruses can directly infect and replicate in human gut tissues.
It is demonstrated that the human gut expresses abundant avian H5N1 receptors, is readily infected ex vivo by the H 5N1 virus, and produces infectious viral particles in organ culture.
Tropism of avian influenza A (H5N1) in the upper and lower respiratory tract
It is demonstrated that ex vivo cultures of human nasopharyngeal, adenoid and tonsillar tissues can be infected with H5N1 viruses in spite of an apparent lack of these receptors.
The role of cell tropism for the pathogenesis of influenza in humans
This review focuses on the factors that, together, determine the cell tropism of influenza viruses, including the receptor specificity of the viral hemagglutinin and the distribution of these receptors in the respiratory tract; the presence of inhibitory factors in the fluid lining the respiratory mucosa; and the requirement for host cell proteases that can cleave the precursor hemag GLUTinin of influenza virus.
Receptor Binding Profiles of Avian Influenza Virus Hemagglutinin Subtypes on Human Cells as a Predictor of Pandemic Potential
It is shown that many avian HA subtypes do not adhere to this canonical view of SA specificity, and the propensity of avian viruses to adapt to human receptors may be more widespread than previously supposed.
Transmission of influenza A/H5N1 viruses in mammals.
A better understanding of the biological basis and genetic determinants that confer transmissibility to H5N1 influenza A viruses in mammals is important to enhance pandemic preparedness.
Adaptation of influenza viruses to human airway receptors
Receptor-binding adaptations underlying the emergence of all prior IAV pandemics in humans are summarized, maintenance and evolution of human-type receptor specificity in subsequent seasonal IAVs, and potential for future human- type receptor adaptation in novel avian HAs are summarized.
Influenza Virus Receptor Specificity and Cell Tropism in Mouse and Human Airway Epithelial Cells
Differences in receptor and cell-specific expression in these species suggest that differentiated human airway epithelial cell cultures may be superior for evaluation of some human strains, while the mouse can provide a model for studying avian strains that preferentially bind only the α2,3-linked SA receptor.
Avian influenza and the implication for human infection
Concern over the pandemic potential of this virus should this transmissibility develop due to its widespread circulation, continued evolution and recent research showing relatively few mutations are needed for airborne mammalian transmission.
The role of receptor binding specificity in interspecies transmission of influenza viruses.
The receptor binding specificity of influenza A viruses is discussed and its role in interspecies transmission is discussed.


Human and avian influenza viruses target different cell types in cultures of human airway epithelium.
It is demonstrated that influenza viruses enter the airway epithelium through specific target cells and that there were striking differences in this respect between human and avian viruses.
Influenza A H5N1 Replication Sites in Humans
In contrast to disseminated infection documented in other mammals and birds, H5N1 viral replication in humans may be restricted to the lung and intestine, and the major site of H5E viruses replication in the lung is the pneumocyte.
Molecular Basis for High Virulence of Hong Kong H5N1 Influenza A Viruses
Using reverse genetics, it is shown that a mutation at position 627 in the PB2 protein influenced the outcome of infection in mice, and high cleavability of the hemagglutinin glycoprotein was an essential requirement for lethal infection.
Sialyloligosaccharides of the respiratory epithelium in the selection of human influenza virus receptor specificity.
Human ciliated tracheal cells appear to contain sialyloligosaccharides preferentially recognized by human influenza strains, suggesting that human H3 influenza strains may have evolved a receptor specificity which favors binding to ciliated cells, and minimizes binding inhibition by respiratory mucus.
Characterization of a Human H5N1 Influenza A Virus Isolated in 2003
The findings portray the HK213 isolate as an aquatic avian influenza A virus without the molecular changes associated with the replication of H5N1 avian viruses in land-based poultry such as chickens.
Genetic analysis of the compatibility between polymerase proteins from human and avian strains of influenza A viruses.
The results showed that replication of the viral-like reporter RNA was more efficient when PB2 and NP were both derived from the same avian or human virus or when PB1 was derived from an avian virus, whatever the origin of the other proteins.
Receptor determinants of human and animal influenza virus isolates: differences in receptor specificity of the H3 hemagglutinin based on species of origin.
The binding of influenza virus to erythrocytes and host cells is mediated by the interaction of the viral hemagglutinin with cell surface receptors containing sialic acid, and receptor specificity appeared, to some extent, to be dependent on the species from which the virus was isolated.
Avian influenza A (H5N1) infection in humans.
The writing committee consisted of the following: John H. Beigel, M.D., National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.; Jeremy Farrar, D.Phil.,