Efficacy of oseltamivir treatment in influenza virus-infected obese mice.
Efficacy of oseltamivir treatment in influenza virus-infected obese mice.
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DOI：
10.1128/mbio.00887-23
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发表时间：
2023-08-31
期刊：
影响因子：
6.4
通讯作者：
Schultz-Cherry, Stacey
中科院分区：
文献类型：
--
作者：
Honce, Rebekah;Jones, Jeremy;Meliopoulos, Victoria A.;Livingston, Brandi;Sharp, Bridgett;Estrada, Leonardo D.;Wang, Lindsey;Caulfield, William;Freeman, Burgess;Govorkova, Elena;Schultz-Cherry, Stacey
从流行病学和经验来看，肥胖与流感感染后更严重的疾病有关。为了缓解严重疾病，建议在感染后几天内开始使用抗病毒药物，如神经氨酸酶抑制剂奥司他韦，特别是在高危宿主。然而，这种治疗可能效果不佳，并可能在处理过的宿主内产生抗药性变异。在这里，我们假设肥胖会降低奥司他韦在遗传性肥胖小鼠模型中的治疗效果。我们证明了奥司他韦治疗不能改善肥胖小鼠的病毒清除。虽然没有出现与奥司他韦耐药性相关的传统变异，但我们确实注意到，药物治疗未能扑灭病毒群体，并在体外确实导致了表型耐药性。总之，这些研究表明，肥胖小鼠独特的发病机制和免疫反应可能对药物干预和流感病毒种群的宿主内动态有意义。流感病毒感染虽然通常在几天到几周内消失，但也可能变得危急，特别是在高危人群中。及时的抗病毒治疗对于减轻这些严重的后遗症至关重要，但人们仍然担心抗病毒治疗对肥胖的宿主是否有效。在这里，我们表明奥司他韦不能改善遗传性肥胖或I型干扰素受体缺陷小鼠的病毒清除。这表明，迟钝的免疫反应可能会削弱奥司他韦的疗效，并使宿主更容易患上严重疾病。这项研究进一步加深了我们对奥司他韦在肥胖小鼠肺部和全身治疗动态的理解，以及奥司他韦治疗对宿主内出现耐药变异的影响。
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. 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.
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影响因子：
6.4
作者：
O'Brien, Kevin B.;Vogel, Peter;Schultz-Cherry, Stacey
通讯作者：
Schultz-Cherry, Stacey
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