Obesity-Related Microenvironment Promotes Emergence of Virulent Influenza Virus Strains

ABSTRACT Obesity is associated with increased disease severity, elevated viral titers in exhaled breath, and significantly prolonged viral shed during influenza A virus infection. Due to the mutable nature of RNA viruses, we questioned whether obesity could also influence influenza virus population...

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Autores principales:	Rebekah Honce, Erik A. Karlsson, Nicholas Wohlgemuth, Leonardo D. Estrada, Victoria A. Meliopoulos, Jiangwei Yao, Stacey Schultz-Cherry
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	NHBE influenza interferons obesity viral evolution virulence Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0f8be709e91242ec8528399106fc710e
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spelling	oai:doaj.org-article:0f8be709e91242ec8528399106fc710e2021-11-15T15:57:03ZObesity-Related Microenvironment Promotes Emergence of Virulent Influenza Virus Strains10.1128/mBio.03341-192150-7511https://doaj.org/article/0f8be709e91242ec8528399106fc710e2020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.03341-19https://doaj.org/toc/2150-7511ABSTRACT Obesity is associated with increased disease severity, elevated viral titers in exhaled breath, and significantly prolonged viral shed during influenza A virus infection. Due to the mutable nature of RNA viruses, we questioned whether obesity could also influence influenza virus population diversity. Here, we show that minor variants rapidly emerge in obese mice. The variants exhibit increased viral replication, resulting in enhanced virulence in wild-type mice. The increased diversity of the viral population correlated with decreased type I interferon responses, and treatment of obese mice with recombinant interferon reduced viral diversity, suggesting that the delayed antiviral response exhibited in obesity permits the emergence of a more virulent influenza virus population. This is not unique to obese mice. Obesity-derived normal human bronchial epithelial (NHBE) cells also showed decreased interferon responses and increased viral replication, suggesting that viral diversity also was impacted in this increasing population. IMPORTANCE Currently, 50% of the adult population worldwide is overweight or obese. In these studies, we demonstrate that obesity not only enhances the severity of influenza infection but also impacts viral diversity. The altered microenvironment associated with obesity supports a more diverse viral quasispecies and affords the emergence of potentially pathogenic variants capable of inducing greater disease severity in lean hosts. This is likely due to the impaired interferon response, which is seen in both obese mice and obesity-derived human bronchial epithelial cells, suggesting that obesity, aside from its impact on influenza virus pathogenesis, permits the stochastic accumulation of potentially pathogenic viral variants, raising concerns about its public health impact as the prevalence of obesity continues to rise.Rebekah HonceErik A. KarlssonNicholas WohlgemuthLeonardo D. EstradaVictoria A. MeliopoulosJiangwei YaoStacey Schultz-CherryAmerican Society for MicrobiologyarticleNHBEinfluenzainterferonsobesityviral evolutionvirulenceMicrobiologyQR1-502ENmBio, Vol 11, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	NHBE influenza interferons obesity viral evolution virulence Microbiology QR1-502
spellingShingle	NHBE influenza interferons obesity viral evolution virulence Microbiology QR1-502 Rebekah Honce Erik A. Karlsson Nicholas Wohlgemuth Leonardo D. Estrada Victoria A. Meliopoulos Jiangwei Yao Stacey Schultz-Cherry Obesity-Related Microenvironment Promotes Emergence of Virulent Influenza Virus Strains
description	ABSTRACT Obesity is associated with increased disease severity, elevated viral titers in exhaled breath, and significantly prolonged viral shed during influenza A virus infection. Due to the mutable nature of RNA viruses, we questioned whether obesity could also influence influenza virus population diversity. Here, we show that minor variants rapidly emerge in obese mice. The variants exhibit increased viral replication, resulting in enhanced virulence in wild-type mice. The increased diversity of the viral population correlated with decreased type I interferon responses, and treatment of obese mice with recombinant interferon reduced viral diversity, suggesting that the delayed antiviral response exhibited in obesity permits the emergence of a more virulent influenza virus population. This is not unique to obese mice. Obesity-derived normal human bronchial epithelial (NHBE) cells also showed decreased interferon responses and increased viral replication, suggesting that viral diversity also was impacted in this increasing population. IMPORTANCE Currently, 50% of the adult population worldwide is overweight or obese. In these studies, we demonstrate that obesity not only enhances the severity of influenza infection but also impacts viral diversity. The altered microenvironment associated with obesity supports a more diverse viral quasispecies and affords the emergence of potentially pathogenic variants capable of inducing greater disease severity in lean hosts. This is likely due to the impaired interferon response, which is seen in both obese mice and obesity-derived human bronchial epithelial cells, suggesting that obesity, aside from its impact on influenza virus pathogenesis, permits the stochastic accumulation of potentially pathogenic viral variants, raising concerns about its public health impact as the prevalence of obesity continues to rise.
format	article
author	Rebekah Honce Erik A. Karlsson Nicholas Wohlgemuth Leonardo D. Estrada Victoria A. Meliopoulos Jiangwei Yao Stacey Schultz-Cherry
author_facet	Rebekah Honce Erik A. Karlsson Nicholas Wohlgemuth Leonardo D. Estrada Victoria A. Meliopoulos Jiangwei Yao Stacey Schultz-Cherry
author_sort	Rebekah Honce
title	Obesity-Related Microenvironment Promotes Emergence of Virulent Influenza Virus Strains
title_short	Obesity-Related Microenvironment Promotes Emergence of Virulent Influenza Virus Strains
title_full	Obesity-Related Microenvironment Promotes Emergence of Virulent Influenza Virus Strains
title_fullStr	Obesity-Related Microenvironment Promotes Emergence of Virulent Influenza Virus Strains
title_full_unstemmed	Obesity-Related Microenvironment Promotes Emergence of Virulent Influenza Virus Strains
title_sort	obesity-related microenvironment promotes emergence of virulent influenza virus strains
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/0f8be709e91242ec8528399106fc710e
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Obesity-Related Microenvironment Promotes Emergence of Virulent Influenza Virus Strains

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