Efficacy of oseltamivir treatment in influenza virus-infected obese mice

Abstract

Obesity has been epidemiologically and empirically linked with more severe diseases upon influenzainfection. 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 effectiveand may generate resistance variants within the treated host. Here, we hypothesized that obesity would reduce oseltamivir treatment effectivenessin 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 influenzavirus population.