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 3H-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.
Highlights
The 1918 influenza, or “Spanish Flu” virus, caused the most devastating pandemic in recorded human history
1918 influenza viral NA was expressed as two inconvertible forms, i.e. active and inactive forms, suggesting an intrinsic difference between the two forms
In this report, using mass spectrometry and in vitro fucosylation, we demonstrated that the inactive form is highly core-fucosylated, whereas the active form is mainly devoid of core fucose
Summary
The 1918 influenza, or “Spanish Flu” virus, caused the most devastating pandemic in recorded human history. Influenza is an ongoing threat to human society [2,3], having caused the recent pandemics of the 2005 Hong Kong avian flu [4] and 2009 swine flu [5]. Research on the 1918 influenza virus may provide key insights for combating the emerging strains of influenza virus. For this reason, the 1918 influenza virus (A/Brevig Mission/1/18) was resurrected from the body of an Alaskan Inuit woman in 2005 [6]. Significant effort has been made to decipher the mechanism of the lethality of this virus since
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