Comparison of oseltamivir and α-galactosylceramide for reducing disease and transmission in pigs infected with 2009 H1N1 pandemic influenza virus
Influenza virus infections are a major cause of respiratory disease in humans. Neuraminidase inhibitors (NAIs) are the primary antiviral medication used to treat ongoing influenza infections. However, NAIs are not always effective for controlling virus shedding and lung inflammation. Other concerns...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Veterinary Science |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fvets.2022.999507/full |
| _version_ | 1811337059246276608 |
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| author | Darling Melany de C. Madrid Weihong Gu Bianca L. Artiaga Guan Yang Julia Loeb Julia Loeb Ian K. Hawkins William L. Castleman John A. Lednicky John A. Lednicky Jürgen A. Richt John P. Driver |
| author_facet | Darling Melany de C. Madrid Weihong Gu Bianca L. Artiaga Guan Yang Julia Loeb Julia Loeb Ian K. Hawkins William L. Castleman John A. Lednicky John A. Lednicky Jürgen A. Richt John P. Driver |
| author_sort | Darling Melany de C. Madrid |
| collection | DOAJ |
| description | Influenza virus infections are a major cause of respiratory disease in humans. Neuraminidase inhibitors (NAIs) are the primary antiviral medication used to treat ongoing influenza infections. However, NAIs are not always effective for controlling virus shedding and lung inflammation. Other concerns are the emergence of NAI-resistant virus strains and the risk of side effects, which are occasionally severe. Consequently, additional anti-influenza therapies to replace or combine with NAIs are desirable. Here, we compared the efficacy of the NAI oseltamivir with the invariant natural killer T (iNKT) cell superagonist, α-galactosylceramide (α-GalCer), which induces innate immune responses that inhibit influenza virus replication in mouse models. We show that oseltamivir reduced lung lesions and lowered virus titers in the upper respiratory tract of pigs infected with A/California/04/2009 (CA04) pandemic H1N1pdm09. It also reduced virus transmission to influenza-naïve contact pigs. In contrast, α-GalCer had no impact on virus replication, lung disease, or virus transmission, even when used in combination with oseltamivir. This is significant as iNKT-cell therapy has been studied as an approach for treating humans with influenza. |
| first_indexed | 2024-04-13T17:49:25Z |
| format | Article |
| id | doaj.art-1327e89a15c44f6abf55a6fe03ea04b8 |
| institution | Directory Open Access Journal |
| issn | 2297-1769 |
| language | English |
| last_indexed | 2024-04-13T17:49:25Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Veterinary Science |
| spelling | doaj.art-1327e89a15c44f6abf55a6fe03ea04b82022-12-22T02:36:47ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692022-10-01910.3389/fvets.2022.999507999507Comparison of oseltamivir and α-galactosylceramide for reducing disease and transmission in pigs infected with 2009 H1N1 pandemic influenza virusDarling Melany de C. Madrid0Weihong Gu1Bianca L. Artiaga2Guan Yang3Julia Loeb4Julia Loeb5Ian K. Hawkins6William L. Castleman7John A. Lednicky8John A. Lednicky9Jürgen A. Richt10John P. Driver11Division of Animal Sciences, University of Missouri, Columbia, MO, United StatesDepartment of Animal Sciences, University of Florida, Gainesville, FL, United StatesDepartment of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, United StatesDepartment of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Environmental and Global Health, University of Florida, Gainesville, FL, United StatesEmerging Pathogens Institute, University of Florida, Gainesville, FL, United StatesDepartment of Comparative, Diagnostic, and Population Medicine, University of Florida, Gainesville, FL, United StatesDepartment of Comparative, Diagnostic, and Population Medicine, University of Florida, Gainesville, FL, United StatesDepartment of Environmental and Global Health, University of Florida, Gainesville, FL, United StatesEmerging Pathogens Institute, University of Florida, Gainesville, FL, United StatesDepartment of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, United StatesDivision of Animal Sciences, University of Missouri, Columbia, MO, United StatesInfluenza virus infections are a major cause of respiratory disease in humans. Neuraminidase inhibitors (NAIs) are the primary antiviral medication used to treat ongoing influenza infections. However, NAIs are not always effective for controlling virus shedding and lung inflammation. Other concerns are the emergence of NAI-resistant virus strains and the risk of side effects, which are occasionally severe. Consequently, additional anti-influenza therapies to replace or combine with NAIs are desirable. Here, we compared the efficacy of the NAI oseltamivir with the invariant natural killer T (iNKT) cell superagonist, α-galactosylceramide (α-GalCer), which induces innate immune responses that inhibit influenza virus replication in mouse models. We show that oseltamivir reduced lung lesions and lowered virus titers in the upper respiratory tract of pigs infected with A/California/04/2009 (CA04) pandemic H1N1pdm09. It also reduced virus transmission to influenza-naïve contact pigs. In contrast, α-GalCer had no impact on virus replication, lung disease, or virus transmission, even when used in combination with oseltamivir. This is significant as iNKT-cell therapy has been studied as an approach for treating humans with influenza.https://www.frontiersin.org/articles/10.3389/fvets.2022.999507/fullα-galactosylceramideantiviralinvariant natural killer T-cellsoseltamivirswineinfluenza |
| spellingShingle | Darling Melany de C. Madrid Weihong Gu Bianca L. Artiaga Guan Yang Julia Loeb Julia Loeb Ian K. Hawkins William L. Castleman John A. Lednicky John A. Lednicky Jürgen A. Richt John P. Driver Comparison of oseltamivir and α-galactosylceramide for reducing disease and transmission in pigs infected with 2009 H1N1 pandemic influenza virus Frontiers in Veterinary Science α-galactosylceramide antiviral invariant natural killer T-cells oseltamivir swine influenza |
| title | Comparison of oseltamivir and α-galactosylceramide for reducing disease and transmission in pigs infected with 2009 H1N1 pandemic influenza virus |
| title_full | Comparison of oseltamivir and α-galactosylceramide for reducing disease and transmission in pigs infected with 2009 H1N1 pandemic influenza virus |
| title_fullStr | Comparison of oseltamivir and α-galactosylceramide for reducing disease and transmission in pigs infected with 2009 H1N1 pandemic influenza virus |
| title_full_unstemmed | Comparison of oseltamivir and α-galactosylceramide for reducing disease and transmission in pigs infected with 2009 H1N1 pandemic influenza virus |
| title_short | Comparison of oseltamivir and α-galactosylceramide for reducing disease and transmission in pigs infected with 2009 H1N1 pandemic influenza virus |
| title_sort | comparison of oseltamivir and α galactosylceramide for reducing disease and transmission in pigs infected with 2009 h1n1 pandemic influenza virus |
| topic | α-galactosylceramide antiviral invariant natural killer T-cells oseltamivir swine influenza |
| url | https://www.frontiersin.org/articles/10.3389/fvets.2022.999507/full |
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