Functional balance between the hemagglutinin and neuraminidase of influenza A(H1N1)pdm09 HA D222 variants.

D222G/N substitutions in A(H1N1)pdm09 hemagglutinin may be associated with increased binding of viruses causing low respiratory tract infections and human pathogenesis. We assessed the impact of such substitutions on the balance between hemagglutinin binding and neuraminidase cleavage, viral growth...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jean-Sébastien Casalegno, Olivier Ferraris, Vanessa Escuret, Maude Bouscambert, Corinne Bergeron, Laetitia Linès, Thierry Excoffier, Martine Valette, Emilie Frobert, Sylvie Pillet, Bruno Pozzetto, Bruno Lina, Michèle Ottmann
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/147a30bbfb6e403eaf9a140e65869f9e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:147a30bbfb6e403eaf9a140e65869f9e
record_format	dspace
spelling	oai:doaj.org-article:147a30bbfb6e403eaf9a140e65869f9e2021-11-25T06:04:54ZFunctional balance between the hemagglutinin and neuraminidase of influenza A(H1N1)pdm09 HA D222 variants.1932-620310.1371/journal.pone.0104009https://doaj.org/article/147a30bbfb6e403eaf9a140e65869f9e2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25119465/?tool=EBIhttps://doaj.org/toc/1932-6203D222G/N substitutions in A(H1N1)pdm09 hemagglutinin may be associated with increased binding of viruses causing low respiratory tract infections and human pathogenesis. We assessed the impact of such substitutions on the balance between hemagglutinin binding and neuraminidase cleavage, viral growth and in vivo virulence.Seven viruses with differing polymorphisms at codon 222 (2 with D, 3 G, 1 N and 1 E) were isolated from patients and characterized with regards hemagglutinin binding affinity (Kd) to α-2,6 sialic acid (SAα-2,6) and SAα-2,3 and neuraminidase enzymatic properties (Km, Ki and Vmax). The hemagglutination assay was used to quantitatively assess the balance between hemagglutinin binding and neuraminidase cleavage. Viral growth properties were compared in vitro in MDCK-SIAT1 cells and in vivo in BALB/c mice. Compared with D222 variants, the binding affinity of G222 variants was greater for SAα-2,3 and lower for SAα-2,6, whereas that of both E222 and N222 variants was greater for both SAα-2,3 and SAα-2,6. Mean neuraminidase activity of D222 variants (16.0 nmol/h/10(6)) was higher than that of G222 (1.7 nmol/h/10(6) viruses) and E/N222 variants (4.4 nmol/h/10(6) viruses). The hemagglutination assay demonstrated a deviation from functional balance by E222 and N222 variants that displayed strong hemagglutinin binding but weak neuraminidase activity. This deviation impaired viral growth in MDCK-SIAT1 cells but not infectivity in mice. All strains but one exhibited low infectious dose in mice (MID50) and replicated to high titers in the lung; this D222 strain exhibited a ten-fold higher MID50 and replicated to low titers. Hemagglutinin-neuraminidase balance status had a greater impact on viral replication than hemagglutinin affinity strength, at least in vitro, thus emphasizing the importance of an optimal balance for influenza virus fitness. The mouse model is effective in assessing binding to SAα-2,3 but cannot differentiate SAα-2,3- from SAα-2,6- preference, nor estimate the hemagglutinin-neuraminidase balance in A(H1N1)pdm09 strains.Jean-Sébastien CasalegnoOlivier FerrarisVanessa EscuretMaude BouscambertCorinne BergeronLaetitia LinèsThierry ExcoffierMartine ValetteEmilie FrobertSylvie PilletBruno PozzettoBruno LinaMichèle OttmannPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e104009 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jean-Sébastien Casalegno Olivier Ferraris Vanessa Escuret Maude Bouscambert Corinne Bergeron Laetitia Linès Thierry Excoffier Martine Valette Emilie Frobert Sylvie Pillet Bruno Pozzetto Bruno Lina Michèle Ottmann Functional balance between the hemagglutinin and neuraminidase of influenza A(H1N1)pdm09 HA D222 variants.
description	D222G/N substitutions in A(H1N1)pdm09 hemagglutinin may be associated with increased binding of viruses causing low respiratory tract infections and human pathogenesis. We assessed the impact of such substitutions on the balance between hemagglutinin binding and neuraminidase cleavage, viral growth and in vivo virulence.Seven viruses with differing polymorphisms at codon 222 (2 with D, 3 G, 1 N and 1 E) were isolated from patients and characterized with regards hemagglutinin binding affinity (Kd) to α-2,6 sialic acid (SAα-2,6) and SAα-2,3 and neuraminidase enzymatic properties (Km, Ki and Vmax). The hemagglutination assay was used to quantitatively assess the balance between hemagglutinin binding and neuraminidase cleavage. Viral growth properties were compared in vitro in MDCK-SIAT1 cells and in vivo in BALB/c mice. Compared with D222 variants, the binding affinity of G222 variants was greater for SAα-2,3 and lower for SAα-2,6, whereas that of both E222 and N222 variants was greater for both SAα-2,3 and SAα-2,6. Mean neuraminidase activity of D222 variants (16.0 nmol/h/10(6)) was higher than that of G222 (1.7 nmol/h/10(6) viruses) and E/N222 variants (4.4 nmol/h/10(6) viruses). The hemagglutination assay demonstrated a deviation from functional balance by E222 and N222 variants that displayed strong hemagglutinin binding but weak neuraminidase activity. This deviation impaired viral growth in MDCK-SIAT1 cells but not infectivity in mice. All strains but one exhibited low infectious dose in mice (MID50) and replicated to high titers in the lung; this D222 strain exhibited a ten-fold higher MID50 and replicated to low titers. Hemagglutinin-neuraminidase balance status had a greater impact on viral replication than hemagglutinin affinity strength, at least in vitro, thus emphasizing the importance of an optimal balance for influenza virus fitness. The mouse model is effective in assessing binding to SAα-2,3 but cannot differentiate SAα-2,3- from SAα-2,6- preference, nor estimate the hemagglutinin-neuraminidase balance in A(H1N1)pdm09 strains.
format	article
author	Jean-Sébastien Casalegno Olivier Ferraris Vanessa Escuret Maude Bouscambert Corinne Bergeron Laetitia Linès Thierry Excoffier Martine Valette Emilie Frobert Sylvie Pillet Bruno Pozzetto Bruno Lina Michèle Ottmann
author_facet	Jean-Sébastien Casalegno Olivier Ferraris Vanessa Escuret Maude Bouscambert Corinne Bergeron Laetitia Linès Thierry Excoffier Martine Valette Emilie Frobert Sylvie Pillet Bruno Pozzetto Bruno Lina Michèle Ottmann
author_sort	Jean-Sébastien Casalegno
title	Functional balance between the hemagglutinin and neuraminidase of influenza A(H1N1)pdm09 HA D222 variants.
title_short	Functional balance between the hemagglutinin and neuraminidase of influenza A(H1N1)pdm09 HA D222 variants.
title_full	Functional balance between the hemagglutinin and neuraminidase of influenza A(H1N1)pdm09 HA D222 variants.
title_fullStr	Functional balance between the hemagglutinin and neuraminidase of influenza A(H1N1)pdm09 HA D222 variants.
title_full_unstemmed	Functional balance between the hemagglutinin and neuraminidase of influenza A(H1N1)pdm09 HA D222 variants.
title_sort	functional balance between the hemagglutinin and neuraminidase of influenza a(h1n1)pdm09 ha d222 variants.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/147a30bbfb6e403eaf9a140e65869f9e
work_keys_str_mv	AT jeansebastiencasalegno functionalbalancebetweenthehemagglutininandneuraminidaseofinfluenzaah1n1pdm09had222variants AT olivierferraris functionalbalancebetweenthehemagglutininandneuraminidaseofinfluenzaah1n1pdm09had222variants AT vanessaescuret functionalbalancebetweenthehemagglutininandneuraminidaseofinfluenzaah1n1pdm09had222variants AT maudebouscambert functionalbalancebetweenthehemagglutininandneuraminidaseofinfluenzaah1n1pdm09had222variants AT corinnebergeron functionalbalancebetweenthehemagglutininandneuraminidaseofinfluenzaah1n1pdm09had222variants AT laetitialines functionalbalancebetweenthehemagglutininandneuraminidaseofinfluenzaah1n1pdm09had222variants AT thierryexcoffier functionalbalancebetweenthehemagglutininandneuraminidaseofinfluenzaah1n1pdm09had222variants AT martinevalette functionalbalancebetweenthehemagglutininandneuraminidaseofinfluenzaah1n1pdm09had222variants AT emiliefrobert functionalbalancebetweenthehemagglutininandneuraminidaseofinfluenzaah1n1pdm09had222variants AT sylviepillet functionalbalancebetweenthehemagglutininandneuraminidaseofinfluenzaah1n1pdm09had222variants AT brunopozzetto functionalbalancebetweenthehemagglutininandneuraminidaseofinfluenzaah1n1pdm09had222variants AT brunolina functionalbalancebetweenthehemagglutininandneuraminidaseofinfluenzaah1n1pdm09had222variants AT micheleottmann functionalbalancebetweenthehemagglutininandneuraminidaseofinfluenzaah1n1pdm09had222variants
_version_	1718414207321374720

Functional balance between the hemagglutinin and neuraminidase of influenza A(H1N1)pdm09 HA D222 variants.

Ejemplares similares