Human-like receptor specificity does not affect the neuraminidase-inhibitor susceptibility of H5N1 influenza viruses.

If highly pathogenic H5N1 influenza viruses acquire affinity for human rather than avian respiratory epithelium, will their susceptibility to neuraminidase (NA) inhibitors (the likely first line of defense against an influenza pandemic) change as well? Adequate pandemic preparedness requires that th...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Natalia A Ilyushina, Elena A Govorkova, Thomas E Gray, Nicolai V Bovin, Robert G Webster
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6c79f36ee75047f6a28de28141e79ebd
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6c79f36ee75047f6a28de28141e79ebd
record_format	dspace
spelling	oai:doaj.org-article:6c79f36ee75047f6a28de28141e79ebd2021-11-25T05:46:38ZHuman-like receptor specificity does not affect the neuraminidase-inhibitor susceptibility of H5N1 influenza viruses.1553-73661553-737410.1371/journal.ppat.1000043https://doaj.org/article/6c79f36ee75047f6a28de28141e79ebd2008-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18404209/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374If highly pathogenic H5N1 influenza viruses acquire affinity for human rather than avian respiratory epithelium, will their susceptibility to neuraminidase (NA) inhibitors (the likely first line of defense against an influenza pandemic) change as well? Adequate pandemic preparedness requires that this question be answered. We generated and tested 31 recombinants of A/Vietnam/1203/04 (H5N1) influenza virus carrying single, double, or triple mutations located within or near the receptor binding site in the hemagglutinin (HA) glycoprotein that alter H5 HA binding affinity or specificity. To gain insight into how combinations of HA and NA mutations can affect the sensitivity of H5N1 virus to NA inhibitors, we also rescued viruses carrying the HA changes together with the H274Y NA substitution, which was reported to confer resistance to the NA inhibitor oseltamivir. Twenty viruses were genetically stable. The triple N158S/Q226L/N248D HA mutation (which eliminates a glycosylation site at position 158) caused a switch from avian to human receptor specificity. In cultures of differentiated human airway epithelial (NHBE) cells, which provide an ex vivo model that recapitulates the receptors in the human respiratory tract, none of the HA-mutant recombinants showed reduced susceptibility to antiviral drugs (oseltamivir or zanamivir). This finding was consistent with the results of NA enzyme inhibition assay, which appears to predict influenza virus susceptibility in vivo. Therefore, acquisition of human-like receptor specificity does not affect susceptibility to NA inhibitors. Sequence analysis of the NA gene alone, rather than analysis of both the NA and HA genes, and phenotypic assays in NHBE cells are likely to adequately identify drug-resistant H5N1 variants isolated from humans during an outbreak.Natalia A IlyushinaElena A GovorkovaThomas E GrayNicolai V BovinRobert G WebsterPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 4, Iss 4, p e1000043 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Natalia A Ilyushina Elena A Govorkova Thomas E Gray Nicolai V Bovin Robert G Webster Human-like receptor specificity does not affect the neuraminidase-inhibitor susceptibility of H5N1 influenza viruses.
description	If highly pathogenic H5N1 influenza viruses acquire affinity for human rather than avian respiratory epithelium, will their susceptibility to neuraminidase (NA) inhibitors (the likely first line of defense against an influenza pandemic) change as well? Adequate pandemic preparedness requires that this question be answered. We generated and tested 31 recombinants of A/Vietnam/1203/04 (H5N1) influenza virus carrying single, double, or triple mutations located within or near the receptor binding site in the hemagglutinin (HA) glycoprotein that alter H5 HA binding affinity or specificity. To gain insight into how combinations of HA and NA mutations can affect the sensitivity of H5N1 virus to NA inhibitors, we also rescued viruses carrying the HA changes together with the H274Y NA substitution, which was reported to confer resistance to the NA inhibitor oseltamivir. Twenty viruses were genetically stable. The triple N158S/Q226L/N248D HA mutation (which eliminates a glycosylation site at position 158) caused a switch from avian to human receptor specificity. In cultures of differentiated human airway epithelial (NHBE) cells, which provide an ex vivo model that recapitulates the receptors in the human respiratory tract, none of the HA-mutant recombinants showed reduced susceptibility to antiviral drugs (oseltamivir or zanamivir). This finding was consistent with the results of NA enzyme inhibition assay, which appears to predict influenza virus susceptibility in vivo. Therefore, acquisition of human-like receptor specificity does not affect susceptibility to NA inhibitors. Sequence analysis of the NA gene alone, rather than analysis of both the NA and HA genes, and phenotypic assays in NHBE cells are likely to adequately identify drug-resistant H5N1 variants isolated from humans during an outbreak.
format	article
author	Natalia A Ilyushina Elena A Govorkova Thomas E Gray Nicolai V Bovin Robert G Webster
author_facet	Natalia A Ilyushina Elena A Govorkova Thomas E Gray Nicolai V Bovin Robert G Webster
author_sort	Natalia A Ilyushina
title	Human-like receptor specificity does not affect the neuraminidase-inhibitor susceptibility of H5N1 influenza viruses.
title_short	Human-like receptor specificity does not affect the neuraminidase-inhibitor susceptibility of H5N1 influenza viruses.
title_full	Human-like receptor specificity does not affect the neuraminidase-inhibitor susceptibility of H5N1 influenza viruses.
title_fullStr	Human-like receptor specificity does not affect the neuraminidase-inhibitor susceptibility of H5N1 influenza viruses.
title_full_unstemmed	Human-like receptor specificity does not affect the neuraminidase-inhibitor susceptibility of H5N1 influenza viruses.
title_sort	human-like receptor specificity does not affect the neuraminidase-inhibitor susceptibility of h5n1 influenza viruses.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/6c79f36ee75047f6a28de28141e79ebd
work_keys_str_mv	AT nataliaailyushina humanlikereceptorspecificitydoesnotaffecttheneuraminidaseinhibitorsusceptibilityofh5n1influenzaviruses AT elenaagovorkova humanlikereceptorspecificitydoesnotaffecttheneuraminidaseinhibitorsusceptibilityofh5n1influenzaviruses AT thomasegray humanlikereceptorspecificitydoesnotaffecttheneuraminidaseinhibitorsusceptibilityofh5n1influenzaviruses AT nicolaivbovin humanlikereceptorspecificitydoesnotaffecttheneuraminidaseinhibitorsusceptibilityofh5n1influenzaviruses AT robertgwebster humanlikereceptorspecificitydoesnotaffecttheneuraminidaseinhibitorsusceptibilityofh5n1influenzaviruses
_version_	1718414461550723072

Human-like receptor specificity does not affect the neuraminidase-inhibitor susceptibility of H5N1 influenza viruses.

Ejemplares similares