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Title: Core-6 fucose and the oligomerization of the 1918 pandemic influenza viral neuraminidase

Abstract

The 1918 H1N1 influenza virus was responsible for one of the most deadly pandemics in human history. Yet to date, the structure component responsible for its virulence is still a mystery. In order to search for such a component, the neuraminidase (NA) antigen of the virus was expressed, which led to the discovery of an active form (tetramer) and an inactive form (dimer and monomer) of the protein due to different glycosylation. In this report, the N-glycans from both forms were released and characterized by mass spectrometry. It was found that the glycans from the active form had 26% core-6 fucosylated, while the glycans from the inactive form had 82% core-6 fucosylated. Even more surprisingly, the stalk region of the active form was almost completely devoid of core-6-linked fucose. These findings were further supported by the results obtained from in vitro incorporation of azido fucose and {sup 3}H-labeled fucose using core-6 fucosyltransferase, FUT8. In addition, the incorporation of fucose did not change the enzymatic activity of the active form, implying that core-6 fucose is not directly involved in the enzymatic activity. It is postulated that core-6 fucose prohibits the oligomerization and subsequent activation of the enzyme. - Graphical abstract: Proposed mechanismmore » for how core-fucose prohibits the tetramerization of the 1918 pandemic viral neuraminidase. Only the cross section of the stalk region with two N-linked glycans are depicted for clarity. (A) Carbohydrate–carbohydrate interaction on non-fucosylated monomer allows tetramerization. (B) Core-fucosylation disrupts the interaction and prevents the tetramerization. - Highlights: • Expressed 1918 pandemic influenza viral neuraminidase has inactive and active forms. • The inactive form contains high level of core-6 fucose, while the active form lacks such modification. • Core fucose could interfere the oligomerization of the neuraminidase and thus its activation. • This discovery may explain why 1918 pandemic influenza caused higher death rate among young population.« less

Authors:
 [1];  [2]
  1. Gregg Hall, UNH Glycomics Center, University of New Hampshire (United States)
  2. Bio-Techne Inc., 614 McKinley Place NE, Minneapolis, MN 55413 (United States)
Publication Date:
OSTI Identifier:
22596364
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 473; Journal Issue: 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIGENS; DEATH; DIMERS; ENZYMES; HEXOSES; IN VITRO; INFLUENZA; INFLUENZA VIRUSES; MASS SPECTROSCOPY; MONOMERS; TRITIUM; VIRULENCE

Citation Formats

Wu, Zhengliang L., E-mail: Leon.wu@bio-techne.com, Zhou, Hui, Ethen, Cheryl M., and Reinhold, Vernon N., E-mail: Vernon.Reinhold@unh.edu. Core-6 fucose and the oligomerization of the 1918 pandemic influenza viral neuraminidase. United States: N. p., 2016. Web. doi:10.1016/J.BBRC.2016.03.096.
Wu, Zhengliang L., E-mail: Leon.wu@bio-techne.com, Zhou, Hui, Ethen, Cheryl M., & Reinhold, Vernon N., E-mail: Vernon.Reinhold@unh.edu. Core-6 fucose and the oligomerization of the 1918 pandemic influenza viral neuraminidase. United States. doi:10.1016/J.BBRC.2016.03.096.
Wu, Zhengliang L., E-mail: Leon.wu@bio-techne.com, Zhou, Hui, Ethen, Cheryl M., and Reinhold, Vernon N., E-mail: Vernon.Reinhold@unh.edu. Fri . "Core-6 fucose and the oligomerization of the 1918 pandemic influenza viral neuraminidase". United States. doi:10.1016/J.BBRC.2016.03.096.
@article{osti_22596364,
title = {Core-6 fucose and the oligomerization of the 1918 pandemic influenza viral neuraminidase},
author = {Wu, Zhengliang L., E-mail: Leon.wu@bio-techne.com and Zhou, Hui and Ethen, Cheryl M. and Reinhold, Vernon N., E-mail: Vernon.Reinhold@unh.edu},
abstractNote = {The 1918 H1N1 influenza virus was responsible for one of the most deadly pandemics in human history. Yet to date, the structure component responsible for its virulence is still a mystery. In order to search for such a component, the neuraminidase (NA) antigen of the virus was expressed, which led to the discovery of an active form (tetramer) and an inactive form (dimer and monomer) of the protein due to different glycosylation. In this report, the N-glycans from both forms were released and characterized by mass spectrometry. It was found that the glycans from the active form had 26% core-6 fucosylated, while the glycans from the inactive form had 82% core-6 fucosylated. Even more surprisingly, the stalk region of the active form was almost completely devoid of core-6-linked fucose. These findings were further supported by the results obtained from in vitro incorporation of azido fucose and {sup 3}H-labeled fucose using core-6 fucosyltransferase, FUT8. In addition, the incorporation of fucose did not change the enzymatic activity of the active form, implying that core-6 fucose is not directly involved in the enzymatic activity. It is postulated that core-6 fucose prohibits the oligomerization and subsequent activation of the enzyme. - Graphical abstract: Proposed mechanism for how core-fucose prohibits the tetramerization of the 1918 pandemic viral neuraminidase. Only the cross section of the stalk region with two N-linked glycans are depicted for clarity. (A) Carbohydrate–carbohydrate interaction on non-fucosylated monomer allows tetramerization. (B) Core-fucosylation disrupts the interaction and prevents the tetramerization. - Highlights: • Expressed 1918 pandemic influenza viral neuraminidase has inactive and active forms. • The inactive form contains high level of core-6 fucose, while the active form lacks such modification. • Core fucose could interfere the oligomerization of the neuraminidase and thus its activation. • This discovery may explain why 1918 pandemic influenza caused higher death rate among young population.},
doi = {10.1016/J.BBRC.2016.03.096},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 473,
place = {United States},
year = {2016},
month = {4}
}