The Hemagglutinin-Esterase Fusion Glycoprotein Is a Primary Determinant of the Exceptional Thermal and Acid Stability of Influenza D Virus

ABSTRACT Influenza D virus (IDV) is unique among four types of influenza viruses in that it utilizes cattle as a primary reservoir. The thermal and acid stability of IDV were examined and directly compared with those of influenza A virus (IAV), influenza B virus (IBV), and influenza C virus (ICV). T...

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Autores principales:	Jieshi Yu, Busha Hika, Runxia Liu, Zizhang Sheng, Ben M. Hause, Feng Li, Dan Wang
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	hemagglutinin-esterase fusion protein acid stability influenza virus thermal stability Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/294db4e30b1447dfb485ce65ffae7d31
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spelling	oai:doaj.org-article:294db4e30b1447dfb485ce65ffae7d312021-11-15T15:22:05ZThe Hemagglutinin-Esterase Fusion Glycoprotein Is a Primary Determinant of the Exceptional Thermal and Acid Stability of Influenza D Virus10.1128/mSphere.00254-172379-5042https://doaj.org/article/294db4e30b1447dfb485ce65ffae7d312017-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00254-17https://doaj.org/toc/2379-5042ABSTRACT Influenza D virus (IDV) is unique among four types of influenza viruses in that it utilizes cattle as a primary reservoir. The thermal and acid stability of IDV were examined and directly compared with those of influenza A virus (IAV), influenza B virus (IBV), and influenza C virus (ICV). The results of our experiments demonstrated that only IDV had a high residual infectivity (~2.5 log units of 50% tissue culture infective dose [TCID50]/ml) after a 60-min exposure to 53°C in solution at a neutral pH, and remarkably, IDV retained this infectivity even after exposure to 53°C for 120 min. Furthermore, the data showed that IDV was extremely resistant to inactivation by low pH. After being treated at pH 3.0 for 30 min, IDV lost only approximately 20% of its original infectiousness, while all other types of influenza viruses were completely inactivated. Finally, replacement of the hemagglutinin (HA) and neuraminidase (NA) proteins of a temperature- and acid-sensitive IAV with the hemagglutinin-esterase fusion (HEF) protein of a stable IDV through a reverse genetic system largely rendered the recombinant IAVs resistant to high-temperature and low-pH treatments. Together, these results indicated that the HEF glycoprotein is a primary determinant of the exceptional temperature and acid tolerance of IDV. Further investigation into the viral entry and fusion mechanism mediated by the intrinsically stable HEF protein of IDV may offer novel insights into how the fusion machinery of influenza viruses evolve to achieve acid and thermal stability, which as a result promotes the potential to transmit across mammal species. IMPORTANCE Influenza D virus (IDV) utilizes cattle as a primary reservoir. Increased outbreaks in pigs and serological evidence of human infection have raised a concern about the potential of IDV adapting to humans. Here, we directly compared IDV’s stability to that of other influenza types (A, B, and C) following prolonged incubation at high temperatures or in a low-pH environment. We found that IDV is the most stable of the four types of influenza viruses. Importantly, we demonstrated that the hemagglutinin-esterase fusion (HEF) protein, which drives the fusion between viral and host cell membranes, is the primary determinant for the high thermal and acid stability of IDV. Considering that there is a link between the acid stability of the hemagglutinin protein of influenza A virus and its cross-species transmission, further investigation of the mechanism of HEF-directed viral tolerance may offer novel insights into tissue tropism and cross-species transmission of influenza viruses.Jieshi YuBusha HikaRunxia LiuZizhang ShengBen M. HauseFeng LiDan WangAmerican Society for Microbiologyarticlehemagglutinin-esterase fusion proteinacid stabilityinfluenza virusthermal stabilityMicrobiologyQR1-502ENmSphere, Vol 2, Iss 4 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	hemagglutinin-esterase fusion protein acid stability influenza virus thermal stability Microbiology QR1-502
spellingShingle	hemagglutinin-esterase fusion protein acid stability influenza virus thermal stability Microbiology QR1-502 Jieshi Yu Busha Hika Runxia Liu Zizhang Sheng Ben M. Hause Feng Li Dan Wang The Hemagglutinin-Esterase Fusion Glycoprotein Is a Primary Determinant of the Exceptional Thermal and Acid Stability of Influenza D Virus
description	ABSTRACT Influenza D virus (IDV) is unique among four types of influenza viruses in that it utilizes cattle as a primary reservoir. The thermal and acid stability of IDV were examined and directly compared with those of influenza A virus (IAV), influenza B virus (IBV), and influenza C virus (ICV). The results of our experiments demonstrated that only IDV had a high residual infectivity (~2.5 log units of 50% tissue culture infective dose [TCID50]/ml) after a 60-min exposure to 53°C in solution at a neutral pH, and remarkably, IDV retained this infectivity even after exposure to 53°C for 120 min. Furthermore, the data showed that IDV was extremely resistant to inactivation by low pH. After being treated at pH 3.0 for 30 min, IDV lost only approximately 20% of its original infectiousness, while all other types of influenza viruses were completely inactivated. Finally, replacement of the hemagglutinin (HA) and neuraminidase (NA) proteins of a temperature- and acid-sensitive IAV with the hemagglutinin-esterase fusion (HEF) protein of a stable IDV through a reverse genetic system largely rendered the recombinant IAVs resistant to high-temperature and low-pH treatments. Together, these results indicated that the HEF glycoprotein is a primary determinant of the exceptional temperature and acid tolerance of IDV. Further investigation into the viral entry and fusion mechanism mediated by the intrinsically stable HEF protein of IDV may offer novel insights into how the fusion machinery of influenza viruses evolve to achieve acid and thermal stability, which as a result promotes the potential to transmit across mammal species. IMPORTANCE Influenza D virus (IDV) utilizes cattle as a primary reservoir. Increased outbreaks in pigs and serological evidence of human infection have raised a concern about the potential of IDV adapting to humans. Here, we directly compared IDV’s stability to that of other influenza types (A, B, and C) following prolonged incubation at high temperatures or in a low-pH environment. We found that IDV is the most stable of the four types of influenza viruses. Importantly, we demonstrated that the hemagglutinin-esterase fusion (HEF) protein, which drives the fusion between viral and host cell membranes, is the primary determinant for the high thermal and acid stability of IDV. Considering that there is a link between the acid stability of the hemagglutinin protein of influenza A virus and its cross-species transmission, further investigation of the mechanism of HEF-directed viral tolerance may offer novel insights into tissue tropism and cross-species transmission of influenza viruses.
format	article
author	Jieshi Yu Busha Hika Runxia Liu Zizhang Sheng Ben M. Hause Feng Li Dan Wang
author_facet	Jieshi Yu Busha Hika Runxia Liu Zizhang Sheng Ben M. Hause Feng Li Dan Wang
author_sort	Jieshi Yu
title	The Hemagglutinin-Esterase Fusion Glycoprotein Is a Primary Determinant of the Exceptional Thermal and Acid Stability of Influenza D Virus
title_short	The Hemagglutinin-Esterase Fusion Glycoprotein Is a Primary Determinant of the Exceptional Thermal and Acid Stability of Influenza D Virus
title_full	The Hemagglutinin-Esterase Fusion Glycoprotein Is a Primary Determinant of the Exceptional Thermal and Acid Stability of Influenza D Virus
title_fullStr	The Hemagglutinin-Esterase Fusion Glycoprotein Is a Primary Determinant of the Exceptional Thermal and Acid Stability of Influenza D Virus
title_full_unstemmed	The Hemagglutinin-Esterase Fusion Glycoprotein Is a Primary Determinant of the Exceptional Thermal and Acid Stability of Influenza D Virus
title_sort	hemagglutinin-esterase fusion glycoprotein is a primary determinant of the exceptional thermal and acid stability of influenza d virus
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/294db4e30b1447dfb485ce65ffae7d31
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The Hemagglutinin-Esterase Fusion Glycoprotein Is a Primary Determinant of the Exceptional Thermal and Acid Stability of Influenza D Virus

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