Sequence dynamics of three influenza A virus strains grown in different MDCK cell lines, including those expressing different sialic acid receptors

2021 ◽  
Author(s):  
Karen N. Barnard ◽  
Brian R. Wasik ◽  
Brynn K. Alford‐Lawrence ◽  
Jessica J. Hayward ◽  
Wendy S. Weichert ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Influenza A Virus ◽  
Cell Lines ◽  
Mdck Cell ◽  
Influenza A ◽  
Sialic Acid Receptors ◽  
Virus Strains

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

2017 ◽  
Vol 91 (11) ◽  
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.

Analysis of the Receptor Specificity of Influenza A Virus Strains Using the Method of Surface Plasmon Resonance

BIOPHYSICS ◽  
2020 ◽  
Vol 65 (2) ◽  
pp. 222-224
Author(s):  
G. S. Onkhonova ◽  
P. Yu. Torzhkova ◽  
V. Yu. Marchenko ◽  
S. V. Svyatchenko ◽  
A. S. Gudymo ◽  
...  
Keyword(s):  
Surface Plasmon Resonance ◽  
Influenza A Virus ◽  
Surface Plasmon ◽  
Plasmon Resonance ◽  
Influenza A ◽  
Receptor Specificity ◽  
Virus Strains

scholarly journals Potent sialic acid inhibitors that target influenza A virus hemagglutinin

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu-Jen Chang ◽  
Cheng-Yun Yeh ◽  
Ju-Chien Cheng ◽  
Yu-Qi Huang ◽  
Kai-Cheng Hsu ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Antiviral Activity ◽  
Binding Site ◽  
Influenza A Virus ◽  
Receptor Binding ◽  
Influenza A ◽  
The United States ◽  
Ligand Complex ◽  
Receptor Binding Site ◽  
Computational Strategy

AbstractEradicating influenza A virus (IAV) is difficult, due to its genetic drift and reassortment ability. As the infectious cycle is initiated by the influenza glycoprotein, hemagglutinin (HA), which mediates the binding of virions to terminal sialic acids moieties, HA is a tempting target of anti-influenza inhibitors. However, the complexity of the HA structure has prevented delineation of the structural characterization of the HA protein–ligand complex. Our computational strategy efficiently analyzed > 200,000 records of compounds held in the United States National Cancer Institute (NCI) database and identified potential HA inhibitors, by modeling the sialic acid (SA) receptor binding site (RBS) for the HA structure. Our modeling revealed that compound NSC85561 showed significant antiviral activity against the IAV H1N1 strain with EC50 values ranging from 2.31 to 2.53 µM and negligible cytotoxicity (CC50 > 700 µM). Using the NSC85561 compound as the template to generate 12 derivatives, robust bioassay results revealed the strongest antiviral efficacies with NSC47715 and NSC7223. Virtual screening clearly identified three SA receptor binding site inhibitors that were successfully validated in experimental data. Thus, our computational strategy has identified SA receptor binding site inhibitors against HA that show IAV-associated antiviral activity.

scholarly journals QUALITATIVE DIFFERENCES IN THE ANTIGENIC COMPOSITION OF INFLUENZA A VIRUS STRAINS

1944 ◽  
Vol 79 (6) ◽  
pp. 633-647 ◽  
Author(s):  
William F. Friedewald
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Serum Antibody ◽  
Allantoic Fluid ◽  
Influenza B Virus ◽  
Influenza B ◽  
Red Cell ◽  
Homologous Virus ◽  
Cell Adsorption ◽  
Virus Strains

A study of the PR8, Christie, Talmey, W.S., and swine strains of influenza A virus by means of antibody absorption tests revealed the following findings: 1. Serum antibody could be specifically absorbed with allantoic fluid containing influenza virus or, more effectively, with concentrated suspensions of virus obtained from allantoic fluid by high-speed centrifugation or by the red cell adsorption and elution technique. Normal allantoic fluid, or the centrifugalized sediment therefrom, failed to absorb antibodies. Influenza B virus (Lee) caused no detectable absorption of antibody from antisera directed against influenza A virus strains, but it specifically absorbed antibody from Lee antisera. 2. The neutralizing, agglutination-inhibiting, and complement-fixing anti-bodies in ferret antisera were completely absorbed only by the homologous virus strain, even though 2 absorptions were carried out with large amounts of heterologous virus strains. 3. PR8 virus appeared to have the broadest range of specific antigenic components for it completely absorbed the heterologous antibodies in Christie and W.S. antisera and left only those antibodies which reacted with the respective homologous strains. The other virus strains (Christie, Talmey, W.S., swine) were more specific in the absorption of heterologous antibodies and completely removed only those antibodies which reacted with the absorbing virus. 4. The absorption tests revealed a higher degree of specificity and individuality of the virus strains than the various cross reactions previously reported. The strain specificity of PR8 virus was equally manifest in absorption tests with ferret sera and with human sera following vaccination. 5. The amount of homologous antibody remaining in a PR8 ferret serum after absorption with PR8 virus, obtained by the red cell adsorption and elution method, varied inversely as the concentration of virus used for absorption. A given concentration of virus, however, absorbed a greater percentage of neutralizing antibodies than either agglutination-inhibiting or complement-fixing antibodies.

scholarly journals Hemagglutinin and neuraminidase matching patterns of two influenza A virus strains related to the 1918 and 2009 global pandemics

2009 ◽  
Vol 387 (2) ◽  
pp. 405-408 ◽  
Author(s):  
Yonghui Zhang ◽  
Xiaojing Lin ◽  
Fengwei Zhang ◽  
Jia Wu ◽  
Wenjie Tan ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Virus Strains
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