Efficacy of oseltamivir treatment in influenza virus-infected obese mice.

Autor:	Honce R; Department of Infectious Diseases, St. Jude Children's Research Hospital , Memphis, Tennessee, USA.; Integrated Program in Biomedical Sciences, University of Tennessee Health Science Center , Memphis, Tennessee, USA., Jones J; Department of Infectious Diseases, St. Jude Children's Research Hospital , Memphis, Tennessee, USA., Meliopoulos VA; Department of Infectious Diseases, St. Jude Children's Research Hospital , Memphis, Tennessee, USA., Livingston B; Department of Infectious Diseases, St. Jude Children's Research Hospital , Memphis, Tennessee, USA., Sharp B; Department of Infectious Diseases, St. Jude Children's Research Hospital , Memphis, Tennessee, USA., Estrada LD; Department of Infectious Diseases, St. Jude Children's Research Hospital , Memphis, Tennessee, USA., Wang L; Preclinical Pharmacokinetic Shared Resource, St. Jude Children's Research Hospital , Memphis, Tennessee, USA., Caulfield W; Preclinical Pharmacokinetic Shared Resource, St. Jude Children's Research Hospital , Memphis, Tennessee, USA., Freeman B; Preclinical Pharmacokinetic Shared Resource, St. Jude Children's Research Hospital , Memphis, Tennessee, USA., Govorkova E; Department of Infectious Diseases, St. Jude Children's Research Hospital , Memphis, Tennessee, USA., Schultz-Cherry S; Department of Infectious Diseases, St. Jude Children's Research Hospital , Memphis, Tennessee, USA.; Integrated Program in Biomedical Sciences, University of Tennessee Health Science Center , Memphis, Tennessee, USA.
Jazyk:	angličtina
Zdroj:	MBio [mBio] 2023 Aug 31; Vol. 14 (4), pp. e0088723. Date of Electronic Publication: 2023 Jun 21.
DOI:	10.1128/mbio.00887-23
Abstrakt:	Obesity has been epidemiologically and empirically linked with more severe diseases upon influenza infection. To ameliorate severe disease, treatment with antivirals, such as the neuraminidase inhibitor oseltamivir, is suggested to begin within days of infection especially in high-risk hosts. However, this treatment can be poorly effective and may generate resistance variants within the treated host. Here, we hypothesized that obesity would reduce oseltamivir treatment effectiveness in the genetically obese mouse model. We demonstrated that oseltamivir treatment does not improve viral clearance in obese mice. While no traditional variants associated with oseltamivir resistance emerged, we did note that drug treatment failed to quench the viral population and did lead to phenotypic drug resistance in vitro . Together, these studies suggest that the unique pathogenesis and immune responses in obese mice could have implications for pharmaceutical interventions and the within-host dynamics of the influenza virus population. IMPORTANCE Influenza virus infections, while typically resolving within days to weeks, can turn critical, especially in high-risk populations. Prompt antiviral administration is crucial to mitigating these severe sequalae, yet concerns remain if antiviral treatment is effective in hosts with obesity. Here, we show that oseltamivir does not improve viral clearance in genetically obese or type I interferon receptor-deficient mice. This suggests a blunted immune response may impair oseltamivir efficacy and render a host more susceptible to severe disease. This study furthers our understanding of oseltamivir treatment dynamics both systemically and in the lungs of obese mice, as well as the consequences of oseltamivir treatment for the within-host emergence of drug-resistant variants. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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