tetano
Editor, Senior Moderator
J Virol. 2017 Mar 29. pii: JVI.02293-16. doi: 10.1128/JVI.02293-16. [Epub ahead of print]
[h=1]Role of Neuraminidase in Influenza A(H7N9) Receptor Binding.[/h] Benton DJ[SUP]1[/SUP], Wharton SA[SUP]1[/SUP], Martin SR[SUP]1[/SUP], McCauley JW[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza A(H7N9) viruses have caused a large number of zoonotic infections since their emergence in 2013. They remain a public health concern due to their repeated high levels of infection and perceived pandemic potential. A major factor that determines influenza A virus fitness and therefore transmissibility is the interaction of the surface glycoproteins haemagglutinin (HA) and neuraminidase (NA) with the cell surface receptor sialic acid. Typically, the HA is responsible for binding to the sialic acid to allow virus internalisation and the NA is a sialidase, responsible for cleaving sialic acid to aid virus spread and release. N9 NA has been previously shown to have receptor binding properties mediated by a sialic acid binding site, which is discrete from the enzymatically active sialidase site, termed the haemadsorption (Hb) site.This study investigates the N9 NA from a zoonotic H7N9 strain in order to determine its possible role in virus receptor binding. We demonstrate that this N9 NA has an active Hb site which binds to sialic acid, which enhances overall virus binding to sialic acid receptor analogues. We also show that the N9 NA can also contribute to receptor binding due to unusual kinetic characteristics of the sialidase site which specifically enhance binding to human-like α2,6-linked sialic acid receptors.Importance The interaction of influenza A virus glycoproteins with cell surface receptors is a major determinant of infectivity and therefore transmissibility. Understanding these interactions is important for understanding which factors are necessary to determine pandemic potential. Influenza A viruses generally mediate binding to cell surface sialic acid receptors via the haemagglutinin (HA) glycoprotein, with the neuraminidase (NA) glycoprotein responsible for cleaving the receptor to allow virus release. Previous studies showed that NA proteins of the N9 subtype can bind sialic acid via a separate binding site, distinct from the sialidase active site. This study demonstrates for purified protein and virus that the NA of the zoonotic viruses H7N9 has binding capacity both via the secondary binding site as well as unusual kinetic properties of the sialidase site which promote receptor binding via this site, which enhance binding to human-like receptors. This could have implications for understanding human-to-human transmission of these viruses.
Copyright ? 2017 Benton et al.
PMID: 28356530 DOI: 10.1128/JVI.02293-16
Free full text
[h=1]Role of Neuraminidase in Influenza A(H7N9) Receptor Binding.[/h] Benton DJ[SUP]1[/SUP], Wharton SA[SUP]1[/SUP], Martin SR[SUP]1[/SUP], McCauley JW[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza A(H7N9) viruses have caused a large number of zoonotic infections since their emergence in 2013. They remain a public health concern due to their repeated high levels of infection and perceived pandemic potential. A major factor that determines influenza A virus fitness and therefore transmissibility is the interaction of the surface glycoproteins haemagglutinin (HA) and neuraminidase (NA) with the cell surface receptor sialic acid. Typically, the HA is responsible for binding to the sialic acid to allow virus internalisation and the NA is a sialidase, responsible for cleaving sialic acid to aid virus spread and release. N9 NA has been previously shown to have receptor binding properties mediated by a sialic acid binding site, which is discrete from the enzymatically active sialidase site, termed the haemadsorption (Hb) site.This study investigates the N9 NA from a zoonotic H7N9 strain in order to determine its possible role in virus receptor binding. We demonstrate that this N9 NA has an active Hb site which binds to sialic acid, which enhances overall virus binding to sialic acid receptor analogues. We also show that the N9 NA can also contribute to receptor binding due to unusual kinetic characteristics of the sialidase site which specifically enhance binding to human-like α2,6-linked sialic acid receptors.Importance The interaction of influenza A virus glycoproteins with cell surface receptors is a major determinant of infectivity and therefore transmissibility. Understanding these interactions is important for understanding which factors are necessary to determine pandemic potential. Influenza A viruses generally mediate binding to cell surface sialic acid receptors via the haemagglutinin (HA) glycoprotein, with the neuraminidase (NA) glycoprotein responsible for cleaving the receptor to allow virus release. Previous studies showed that NA proteins of the N9 subtype can bind sialic acid via a separate binding site, distinct from the sialidase active site. This study demonstrates for purified protein and virus that the NA of the zoonotic viruses H7N9 has binding capacity both via the secondary binding site as well as unusual kinetic properties of the sialidase site which promote receptor binding via this site, which enhance binding to human-like receptors. This could have implications for understanding human-to-human transmission of these viruses.
Copyright ? 2017 Benton et al.
PMID: 28356530 DOI: 10.1128/JVI.02293-16
Free full text