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...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2020-04-01
|
| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.03341-19 |
| _version_ | 1818346817113292800 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-13T17:24:17Z |
| format | Article |
| id | doaj.art-0f8be709e91242ec8528399106fc710e |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-13T17:24:17Z |
| publishDate | 2020-04-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-0f8be709e91242ec8528399106fc710e2022-12-21T23:37:14ZengAmerican Society for MicrobiologymBio2150-75112020-04-0111210.1128/mBio.03341-19Obesity-Related Microenvironment Promotes Emergence of Virulent Influenza Virus StrainsRebekah Honce0Erik A. Karlsson1Nicholas Wohlgemuth2Leonardo D. Estrada3Victoria A. Meliopoulos4Jiangwei Yao5Stacey Schultz-Cherry6Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, USADepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, USADepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, USADepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, USADepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, USADepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, USADepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, USAABSTRACT 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.https://journals.asm.org/doi/10.1128/mBio.03341-19NHBEinfluenzainterferonsobesityviral evolutionvirulence |
| spellingShingle | 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 mBio NHBE influenza interferons obesity viral evolution virulence |
| title | 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_short | Obesity-Related Microenvironment Promotes Emergence of Virulent Influenza Virus Strains |
| title_sort | obesity related microenvironment promotes emergence of virulent influenza virus strains |
| topic | NHBE influenza interferons obesity viral evolution virulence |
| url | https://journals.asm.org/doi/10.1128/mBio.03341-19 |
| work_keys_str_mv | AT rebekahhonce obesityrelatedmicroenvironmentpromotesemergenceofvirulentinfluenzavirusstrains AT erikakarlsson obesityrelatedmicroenvironmentpromotesemergenceofvirulentinfluenzavirusstrains AT nicholaswohlgemuth obesityrelatedmicroenvironmentpromotesemergenceofvirulentinfluenzavirusstrains AT leonardodestrada obesityrelatedmicroenvironmentpromotesemergenceofvirulentinfluenzavirusstrains AT victoriaameliopoulos obesityrelatedmicroenvironmentpromotesemergenceofvirulentinfluenzavirusstrains AT jiangweiyao obesityrelatedmicroenvironmentpromotesemergenceofvirulentinfluenzavirusstrains AT staceyschultzcherry obesityrelatedmicroenvironmentpromotesemergenceofvirulentinfluenzavirusstrains |