Relationship between hemagglutinin stability and influenza virus persistence after exposure to low pH or supraphysiological heating.

The hemagglutinin (HA) surface glycoprotein is triggered by endosomal low pH to cause membrane fusion during influenza A virus (IAV) entry yet must remain sufficiently stable to avoid premature activation during virion transit between cells and hosts. HA activation pH and/or virion inactivation pH v...

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Autores principales:	Guohua Yang, Chet R Ojha, Charles J Russell
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/2fd411c54790405ba57981eea02ba9eb
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spelling	oai:doaj.org-article:2fd411c54790405ba57981eea02ba9eb2021-12-02T20:00:13ZRelationship between hemagglutinin stability and influenza virus persistence after exposure to low pH or supraphysiological heating.1553-73661553-737410.1371/journal.ppat.1009910https://doaj.org/article/2fd411c54790405ba57981eea02ba9eb2021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009910https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The hemagglutinin (HA) surface glycoprotein is triggered by endosomal low pH to cause membrane fusion during influenza A virus (IAV) entry yet must remain sufficiently stable to avoid premature activation during virion transit between cells and hosts. HA activation pH and/or virion inactivation pH values less than pH 5.6 are thought to be required for IAV airborne transmissibility and human pandemic potential. To enable higher-throughput screening of emerging IAV strains for "humanized" stability, we developed a luciferase reporter assay that measures the threshold pH at which IAVs are inactivated. The reporter assay yielded results similar to TCID50 assay yet required one-fourth the time and one-tenth the virus. For four A/TN/09 (H1N1) HA mutants and 73 IAVs of varying subtype, virion inactivation pH was compared to HA activation pH and the rate of inactivation during 55°C heating. HA stability values correlated highly with virion acid and thermal stability values for isogenic viruses containing HA point mutations. HA stability also correlated with virion acid stability for human isolates but did not correlate with thermal stability at 55°C, raising doubt in the use of supraphysiological heating assays. Some animal isolates had virion inactivation pH values lower than HA activation pH, suggesting factors beyond HA stability can modulate virion stability. The coupling of HA activation pH and virion inactivation pH, and at a value below 5.6, was associated with human adaptation. This suggests that both virologic properties should be considered in risk assessment algorithms for pandemic potential.Guohua YangChet R OjhaCharles J RussellPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 9, p e1009910 (2021)
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 Guohua Yang Chet R Ojha Charles J Russell Relationship between hemagglutinin stability and influenza virus persistence after exposure to low pH or supraphysiological heating.
description	The hemagglutinin (HA) surface glycoprotein is triggered by endosomal low pH to cause membrane fusion during influenza A virus (IAV) entry yet must remain sufficiently stable to avoid premature activation during virion transit between cells and hosts. HA activation pH and/or virion inactivation pH values less than pH 5.6 are thought to be required for IAV airborne transmissibility and human pandemic potential. To enable higher-throughput screening of emerging IAV strains for "humanized" stability, we developed a luciferase reporter assay that measures the threshold pH at which IAVs are inactivated. The reporter assay yielded results similar to TCID50 assay yet required one-fourth the time and one-tenth the virus. For four A/TN/09 (H1N1) HA mutants and 73 IAVs of varying subtype, virion inactivation pH was compared to HA activation pH and the rate of inactivation during 55°C heating. HA stability values correlated highly with virion acid and thermal stability values for isogenic viruses containing HA point mutations. HA stability also correlated with virion acid stability for human isolates but did not correlate with thermal stability at 55°C, raising doubt in the use of supraphysiological heating assays. Some animal isolates had virion inactivation pH values lower than HA activation pH, suggesting factors beyond HA stability can modulate virion stability. The coupling of HA activation pH and virion inactivation pH, and at a value below 5.6, was associated with human adaptation. This suggests that both virologic properties should be considered in risk assessment algorithms for pandemic potential.
format	article
author	Guohua Yang Chet R Ojha Charles J Russell
author_facet	Guohua Yang Chet R Ojha Charles J Russell
author_sort	Guohua Yang
title	Relationship between hemagglutinin stability and influenza virus persistence after exposure to low pH or supraphysiological heating.
title_short	Relationship between hemagglutinin stability and influenza virus persistence after exposure to low pH or supraphysiological heating.
title_full	Relationship between hemagglutinin stability and influenza virus persistence after exposure to low pH or supraphysiological heating.
title_fullStr	Relationship between hemagglutinin stability and influenza virus persistence after exposure to low pH or supraphysiological heating.
title_full_unstemmed	Relationship between hemagglutinin stability and influenza virus persistence after exposure to low pH or supraphysiological heating.
title_sort	relationship between hemagglutinin stability and influenza virus persistence after exposure to low ph or supraphysiological heating.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/2fd411c54790405ba57981eea02ba9eb
work_keys_str_mv	AT guohuayang relationshipbetweenhemagglutininstabilityandinfluenzaviruspersistenceafterexposuretolowphorsupraphysiologicalheating AT chetrojha relationshipbetweenhemagglutininstabilityandinfluenzaviruspersistenceafterexposuretolowphorsupraphysiologicalheating AT charlesjrussell relationshipbetweenhemagglutininstabilityandinfluenzaviruspersistenceafterexposuretolowphorsupraphysiologicalheating
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Relationship between hemagglutinin stability and influenza virus persistence after exposure to low pH or supraphysiological heating.

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