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Interplay between H1N1 influenza a virus infection, extracellular and intracellular respiratory tract pH, and host responses in a mouse model
During influenza A virus (IAV) entry, the hemagglutinin (HA) protein is triggered by endosomal low pH to undergo irreversible structural changes that mediate membrane fusion. HA proteins from different isolates vary in the pH at which they become activated in endosomes or become irreversible inactiv...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115840/ https://www.ncbi.nlm.nih.gov/pubmed/33979408 http://dx.doi.org/10.1371/journal.pone.0251473 |
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author | Okda, Faten A. Perry, S. Scott Webby, Richard J. Russell, Charles J. |
author_facet | Okda, Faten A. Perry, S. Scott Webby, Richard J. Russell, Charles J. |
author_sort | Okda, Faten A. |
collection | PubMed |
description | During influenza A virus (IAV) entry, the hemagglutinin (HA) protein is triggered by endosomal low pH to undergo irreversible structural changes that mediate membrane fusion. HA proteins from different isolates vary in the pH at which they become activated in endosomes or become irreversible inactivated if exposed to extracellular acid. Little is known about extracellular pH in the upper respiratory tracts of mammals, how pH may shift during IAV infection, and its impact on replication of viruses that vary in HA activation pH. Here, we inoculated DBA/2J mice intranasally with A/TN/1-560/2009 (H1N1) (activation pH 5.5) or a mutant containing the destabilizing mutation HA1-Y17H (pH 6.0). We measured the kinetics of extracellular pH during infection using an optical pH-sensitive microsensor probe placed in the naris, nasal sinus, soft palate, and trachea. We also measured intracellular pH of single-cell suspensions of live, primary lung epithelial cells with various wavelength pH-sensitive dyes localized to cell membranes, cytosol, endosomes, secretory vesicles, microtubules, and lysosomes. Infection with either virus decreased extracellular pH and increased intracellular pH. Peak host immune responses were observed at 2 days post infection (DPI) and peak pH changes at 5 DPI. Extracellular and intracellular pH returned to baseline by 7 DPI in mice infected with HA1-Y17H and was restored later in wildtype-infected. Overall, IAV infection altered respiratory tract pH, which in turn modulated replication efficiency. This suggests a virus-host pH feedback loop that may select for IAV strains containing HA proteins of optimal pH stability, which may be approximately pH 5.5 in mice but may differ in other species. |
format | Online Article Text |
id | pubmed-8115840 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-81158402021-05-24 Interplay between H1N1 influenza a virus infection, extracellular and intracellular respiratory tract pH, and host responses in a mouse model Okda, Faten A. Perry, S. Scott Webby, Richard J. Russell, Charles J. PLoS One Research Article During influenza A virus (IAV) entry, the hemagglutinin (HA) protein is triggered by endosomal low pH to undergo irreversible structural changes that mediate membrane fusion. HA proteins from different isolates vary in the pH at which they become activated in endosomes or become irreversible inactivated if exposed to extracellular acid. Little is known about extracellular pH in the upper respiratory tracts of mammals, how pH may shift during IAV infection, and its impact on replication of viruses that vary in HA activation pH. Here, we inoculated DBA/2J mice intranasally with A/TN/1-560/2009 (H1N1) (activation pH 5.5) or a mutant containing the destabilizing mutation HA1-Y17H (pH 6.0). We measured the kinetics of extracellular pH during infection using an optical pH-sensitive microsensor probe placed in the naris, nasal sinus, soft palate, and trachea. We also measured intracellular pH of single-cell suspensions of live, primary lung epithelial cells with various wavelength pH-sensitive dyes localized to cell membranes, cytosol, endosomes, secretory vesicles, microtubules, and lysosomes. Infection with either virus decreased extracellular pH and increased intracellular pH. Peak host immune responses were observed at 2 days post infection (DPI) and peak pH changes at 5 DPI. Extracellular and intracellular pH returned to baseline by 7 DPI in mice infected with HA1-Y17H and was restored later in wildtype-infected. Overall, IAV infection altered respiratory tract pH, which in turn modulated replication efficiency. This suggests a virus-host pH feedback loop that may select for IAV strains containing HA proteins of optimal pH stability, which may be approximately pH 5.5 in mice but may differ in other species. Public Library of Science 2021-05-12 /pmc/articles/PMC8115840/ /pubmed/33979408 http://dx.doi.org/10.1371/journal.pone.0251473 Text en © 2021 Okda et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Okda, Faten A. Perry, S. Scott Webby, Richard J. Russell, Charles J. Interplay between H1N1 influenza a virus infection, extracellular and intracellular respiratory tract pH, and host responses in a mouse model |
title | Interplay between H1N1 influenza a virus infection, extracellular and intracellular respiratory tract pH, and host responses in a mouse model |
title_full | Interplay between H1N1 influenza a virus infection, extracellular and intracellular respiratory tract pH, and host responses in a mouse model |
title_fullStr | Interplay between H1N1 influenza a virus infection, extracellular and intracellular respiratory tract pH, and host responses in a mouse model |
title_full_unstemmed | Interplay between H1N1 influenza a virus infection, extracellular and intracellular respiratory tract pH, and host responses in a mouse model |
title_short | Interplay between H1N1 influenza a virus infection, extracellular and intracellular respiratory tract pH, and host responses in a mouse model |
title_sort | interplay between h1n1 influenza a virus infection, extracellular and intracellular respiratory tract ph, and host responses in a mouse model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115840/ https://www.ncbi.nlm.nih.gov/pubmed/33979408 http://dx.doi.org/10.1371/journal.pone.0251473 |
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