Sialic Acid Receptors of Viruses

Infection by the influenza virus depends firstly on cell adhesion via the sialic-acid-binding viral surface protein, haemagglutinin, and secondly on the successful escape of progeny viruses from the host cell to enable the virus to spread to other cells. To achieve the latter, influenza uses another glycoprotein, the enzyme neuraminidase (NA), to cleave the sialic acid receptors from the surface of the original host cell. This paper traces the development of anti-influenza drugs, from the initial suggestion by MacFarlane Burnet in 1948 that an effective ‘competitive poison’ of the virus' NA might be useful in controlling infection by the virus, through to the determination of the structure of NA by X-ray crystallography and the realization of Burnet's idea with the design of NA inhibitors. A focus is the contribution of the late William Graeme Laver, FRS, to this research.

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Combinatorial design of a sialic acid imprinted binding site exploring a dual ion receptor approach

RSC Advances ◽

10.1039/d1ra06962d ◽

2021 ◽

Vol 11 (54) ◽

pp. 34329-34337

Author(s):

Liliia Mavliutova ◽

Elena Verduci ◽

Börje Sellergren

Keyword(s):

Sialic Acid ◽

Crown Ether ◽

Binding Site ◽

Combinatorial Design ◽

Sialic Acid Receptors ◽

Ion Imprinting

Dual-ion imprinting of sialic acid via cooperatively acting ureido- and crown ether functionalities leads to charge neutral sialic acid receptors with strong sialoglycopeptide affinity.

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Direct and label-free influenza virus detection based on multisite binding to sialic acid receptors

Biosensors and Bioelectronics ◽

10.1016/j.bios.2017.02.023 ◽

2017 ◽

Vol 92 ◽

pp. 234-240 ◽

Cited By ~ 14

Author(s):

Yukichi Horiguchi ◽

Tatsuro Goda ◽

Akira Matsumoto ◽

Hiroaki Takeuchi ◽

Shoji Yamaoka ◽

...

Keyword(s):

Influenza Virus ◽

Sialic Acid ◽

Virus Detection ◽

Label Free ◽

Sialic Acid Receptors ◽

Influenza Virus Detection

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Exploring Sialic Acid Receptors-Related Infection Behavior of Avian Influenza Virus in Human Bronchial Epithelial Cells by Single-Particle Tracking

Small ◽

10.1002/smll.201303532 ◽

2014 ◽

Vol 10 (13) ◽

pp. 2712-2720 ◽

Cited By ~ 13

Author(s):

Zhi-Gang Wang ◽

Shu-Lin Liu ◽

Zhi-Ling Zhang ◽

Zhi-Quan Tian ◽

Hong-Wu Tang ◽

...

Keyword(s):

Influenza Virus ◽

Sialic Acid ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Particle Tracking ◽

Single Particle ◽

Single Particle Tracking ◽

Human Bronchial Epithelial Cells ◽

Bronchial Epithelial ◽

Sialic Acid Receptors

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Distribution of sialic acid receptors and experimental infections with different subtypes of influenza A viruses in Qinghai-Tibet plateau wild pika

Virology Journal ◽

10.1186/s12985-015-0290-8 ◽

2015 ◽

Vol 12 (1) ◽

Cited By ~ 6

Author(s):

Yan Li ◽

Haixia Xiao ◽

Chaobin Huang ◽

Haigang Sun ◽

Laixing Li ◽

...

Keyword(s):

Sialic Acid ◽

Influenza A ◽

Tibet Plateau ◽

Influenza A Viruses ◽

Experimental Infections ◽

Sialic Acid Receptors ◽

Qinghai Tibet Plateau

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Role of Neuraminidase in Influenza A(H7N9) Virus Receptor Binding

Journal of Virology ◽

10.1128/jvi.02293-16 ◽

2017 ◽

Vol 91 (11) ◽

Cited By ~ 31

Author(s):

Donald J. Benton ◽

Stephen A. Wharton ◽

Stephen R. Martin ◽

John W. McCauley

Keyword(s):

Sialic Acid ◽

Cell Surface ◽

Binding Site ◽

Influenza A Virus ◽

Receptor Binding ◽

Influenza A ◽

Health Concern ◽

H7n9 Virus ◽

Virus Receptor ◽

Sialic Acid Receptors

ABSTRACT 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 the repeated high levels of infection with these viruses and their perceived pandemic potential. A major factor that determines influenza A virus fitness and therefore transmissibility is the interaction of the surface glycoproteins hemagglutinin (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 internalization and the NA is a sialidase responsible for cleaving sialic acid to aid virus spread and release. N9 NA has previously been shown to have receptor binding properties mediated by a sialic acid binding site, termed the hemadsorption (Hb) site, which is discrete from the enzymatically active sialidase site. This study investigated the N9 NA from a zoonotic H7N9 virus 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 hemagglutinin (HA) glycoprotein, with the neuraminidase (NA) glycoprotein being responsible for cleaving the receptor to allow virus release. Previous studies showed that the 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 H7N9 viruses has a binding capacity via both the secondary binding site and unusual kinetic properties of the sialidase site which promote receptor binding via this site and which enhance binding to human-like receptors. This could have implications for understanding human-to-human transmission of these viruses.

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Second Sialic Acid Binding Site in Newcastle Disease Virus Hemagglutinin-Neuraminidase: Implications for Fusion

Journal of Virology ◽

10.1128/jvi.78.7.3733-3741.2004 ◽

2004 ◽

Vol 78 (7) ◽

pp. 3733-3741 ◽

Cited By ~ 124

Author(s):

Viatcheslav Zaitsev ◽

Mark von Itzstein ◽

Darrin Groves ◽

Milton Kiefel ◽

Toru Takimoto ◽

...

Keyword(s):

Sialic Acid ◽

Newcastle Disease Virus ◽

Binding Site ◽

Disease Virus ◽

Newcastle Disease ◽

Surface Glycoprotein ◽

Crystal Forms ◽

Sialic Acid Receptors ◽

Sialic Acid Binding ◽

Infected Cells

ABSTRACT Paramyxoviruses are the leading cause of respiratory disease in children. Several paramyxoviruses possess a surface glycoprotein, the hemagglutinin-neuraminidase (HN), that is involved in attachment to sialic acid receptors, promotion of fusion, and removal of sialic acid from infected cells and progeny virions. Previously we showed that Newcastle disease virus (NDV) HN contained a pliable sialic acid recognition site that could take two states, a binding state and a catalytic state. Here we present evidence for a second sialic acid binding site at the dimer interface of HN and present a model for its involvement in cell fusion. Three different crystal forms of NDV HN now reveal identical tetrameric arrangements of HN monomers, perhaps indicative of the tetramer association found on the viral surface.

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