Sialobiology of Influenza: Molecular Mechanism of Host Range Variation of Influenza Viruses

Abstract

The gene pool of influenza A viruses in aquatic birds provides all of the genetic diversity required for human and lower animals. Host range selection of the receptor binding specificity of the influenza virus hemagglutinin occurs during maintenance of the virus in different host cells that express different receptor sialo-sugar chains. In this paper, functional roles of the hemagglutinin and neuraminidase spikes of influenza viruses are described in the relation to 1) host range of influenza viruses, 2) receptor binding specificity of human and other animal influenza viruses, 3) recognition of sialyl sugar chains by Spanish influenza virus hemagglutinin, 4) highly pathogenic and potentially pandemic H5N1, H9N2, and H7N7 avian influenza viruses and molecular mechanism of host range variation of influenza viruses, 5) role of the neuraminidase spike for the host range of influenza viruses, and 6) Development of anti-influenza drugs.

The Role of Sialylated Glycans in Human Platelet Endothelial Cell Adhesion Molecule 1 (PECAM-1)-mediated Trans Homophilic Interactions and Endothelial Cell Barrier Function

“…The nature of the linkage can matter a great deal, as it defines an important level of specificity in protein/carbohydrate recognition, with each isoform presenting a unique three-dimensional spatial configuration to the cell surface receptors with which they interact. Thus, human Sialoadhesin (Siglec 1/CD169) (41, 42), Myelinassociated glycoprotein (Siglec 4) (43), and avian influenza virus hemagglutinin (44,45) prefer glycans that terminate with ␣2,3 sialic acid, whereas the human influenza virus hemagglutinin (44,45), the Ig superfamily member CD22 (Siglec 2) (46), and murine PECAM-1 (20) all bind with higher affinity to ␣2,6-linked sialic acids.…”

A gel-capture assay for characterizing the sialyl-glycan selectivity of influenza viruses

“…The surface HA of influenza viruses initiates virus internalization by binding to the SA attached to membrane glycoproteins, glycophospholipids, and proteoglycans (Skehel and Wiley, 2000;Suzuki, 2005). The host receptor distribution and sialyl-glycan linkage (α 2,6 or α 2,3) specificity of the viral HA largely determines a host range of the virus (Skehel and Wiley, 2000;Suzuki, 2005).…”

“…The host receptor distribution and sialyl-glycan linkage (α 2,6 or α 2,3) specificity of the viral HA largely determines a host range of the virus (Skehel and Wiley, 2000;Suzuki, 2005). HA of avian influenza viruses usually display a preference for α2-3-linked sialyl-glycans, whereas HA of human influenza viruses preferentially bind α2-6-linked sialyl-glycans (Skehel and Wiley, 2000;Gamblin et al, 2004;Suzuki, 2005;Stevens et al, 2006b). Human influenza B and swine influenza A viruses have been reported to bind both α2,3 and α2,6-linked sialyl-glycans (Ito et al, 1998;Gamblin et al, 2004;Wang et al, 2007;Childs et al, 2009;Maines et al, 2009).…”

Requirement for Siva-1 for replication of influenza A virus through apoptosis induction

“…The estimated death rate from seasonal flu is less than 0.1 % of infected patients, and the virus causing seasonal flu is relatively weaker than the virus that has caused pandemics in the past. However, it is estimated that about 250 000-500 000 patients still succumb to seasonal flu every year worldwide (Suzuki, 2005). Influenza A virus may also be a cause of lethal infectious diseases culminating in severe pneumonia.…”