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Bovine Lactoferrin Prevents Influenza A Virus Infection by Interfering with the Fusogenic Function of Viral Hemagglutinin

Bovine lactoferrin (bLf) is an iron-binding glycoprotein folded in two symmetric globular lobes (N- and C-lobes) with potent antimicrobial and immunomodulatory activities. Recently, we have shown that bLf, and in particular its C-lobe, interacts with influenza A virus hemagglutinin and prevents infe...

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Autores principales: Superti, Fabiana, Agamennone, Mariangela, Pietrantoni, Agostina, Ammendolia, Maria Grazia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357187/
https://www.ncbi.nlm.nih.gov/pubmed/30641890
http://dx.doi.org/10.3390/v11010051
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author Superti, Fabiana
Agamennone, Mariangela
Pietrantoni, Agostina
Ammendolia, Maria Grazia
author_facet Superti, Fabiana
Agamennone, Mariangela
Pietrantoni, Agostina
Ammendolia, Maria Grazia
author_sort Superti, Fabiana
collection PubMed
description Bovine lactoferrin (bLf) is an iron-binding glycoprotein folded in two symmetric globular lobes (N- and C-lobes) with potent antimicrobial and immunomodulatory activities. Recently, we have shown that bLf, and in particular its C-lobe, interacts with influenza A virus hemagglutinin and prevents infection by different H1 and H3 viral subtypes. Influenza virus hemagglutinin (HA), and in particular its highly conserved fusion peptide involved in the low-pH-mediated fusion process, plays a significant role in the early steps of viral infection and represents an attractive target for the development of anti-influenza drugs. In the present research, we further investigated the influence of low pH on the interactions between bLf and influenza A H1N1 virus by different techniques, such as enzyme-linked immunosorbent assay, electron microscopy, hemolysis inhibition assay, and time course assay. Our results demonstrate that lactoferrin interaction with influenza hemagglutinin at low pH induces alterations that stabilize the conformation of the hemagglutinin, resulting in the inhibition of the fusion peptide activity. Taken together, our data allowed to better characterize the HA-specific inhibiting activity of bLf and to confirm HA as a good target for drug development.
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spelling pubmed-63571872019-02-05 Bovine Lactoferrin Prevents Influenza A Virus Infection by Interfering with the Fusogenic Function of Viral Hemagglutinin Superti, Fabiana Agamennone, Mariangela Pietrantoni, Agostina Ammendolia, Maria Grazia Viruses Article Bovine lactoferrin (bLf) is an iron-binding glycoprotein folded in two symmetric globular lobes (N- and C-lobes) with potent antimicrobial and immunomodulatory activities. Recently, we have shown that bLf, and in particular its C-lobe, interacts with influenza A virus hemagglutinin and prevents infection by different H1 and H3 viral subtypes. Influenza virus hemagglutinin (HA), and in particular its highly conserved fusion peptide involved in the low-pH-mediated fusion process, plays a significant role in the early steps of viral infection and represents an attractive target for the development of anti-influenza drugs. In the present research, we further investigated the influence of low pH on the interactions between bLf and influenza A H1N1 virus by different techniques, such as enzyme-linked immunosorbent assay, electron microscopy, hemolysis inhibition assay, and time course assay. Our results demonstrate that lactoferrin interaction with influenza hemagglutinin at low pH induces alterations that stabilize the conformation of the hemagglutinin, resulting in the inhibition of the fusion peptide activity. Taken together, our data allowed to better characterize the HA-specific inhibiting activity of bLf and to confirm HA as a good target for drug development. MDPI 2019-01-11 /pmc/articles/PMC6357187/ /pubmed/30641890 http://dx.doi.org/10.3390/v11010051 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Superti, Fabiana
Agamennone, Mariangela
Pietrantoni, Agostina
Ammendolia, Maria Grazia
Bovine Lactoferrin Prevents Influenza A Virus Infection by Interfering with the Fusogenic Function of Viral Hemagglutinin
title Bovine Lactoferrin Prevents Influenza A Virus Infection by Interfering with the Fusogenic Function of Viral Hemagglutinin
title_full Bovine Lactoferrin Prevents Influenza A Virus Infection by Interfering with the Fusogenic Function of Viral Hemagglutinin
title_fullStr Bovine Lactoferrin Prevents Influenza A Virus Infection by Interfering with the Fusogenic Function of Viral Hemagglutinin
title_full_unstemmed Bovine Lactoferrin Prevents Influenza A Virus Infection by Interfering with the Fusogenic Function of Viral Hemagglutinin
title_short Bovine Lactoferrin Prevents Influenza A Virus Infection by Interfering with the Fusogenic Function of Viral Hemagglutinin
title_sort bovine lactoferrin prevents influenza a virus infection by interfering with the fusogenic function of viral hemagglutinin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357187/
https://www.ncbi.nlm.nih.gov/pubmed/30641890
http://dx.doi.org/10.3390/v11010051
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