Staphylococcus aureus Lipase 1 Enhances Influenza A Virus Replication

Abstract

Influenza A virus (IAV) causes annual epidemics of respiratory disease in humans, often complicated by secondary coinfection with bacterial pathogens such as <i>Staphylococcus aureus</i> Here, we report that the <i>S. aureus</i> secreted protein lipase 1 enhances IAV replication <i>in vitro</i> in primary cells, including human lung fibroblasts. The proviral activity of lipase 1 is dependent on its enzymatic function, acts late in the viral life cycle, and results in increased infectivity through positive modulation of virus budding. Furthermore, the proviral effect of lipase 1 on IAV is exhibited during <i>in vivo</i> infection of embryonated hen's eggs and, importantly, increases the yield of a vaccine strain of IAV by approximately 5-fold. Thus, we have identified the first <i>S. aureus</i> protein to enhance IAV replication, suggesting a potential role in coinfection. Importantly, this activity may be harnessed to address global shortages of influenza vaccines.<b>IMPORTANCE</b> Influenza A virus (IAV) causes annual epidemics and sporadic pandemics of respiratory disease. Secondary bacterial coinfection by organisms such as <i>Staphylococcus aureus</i> is the most common complication of primary IAV infection and is associated with high levels of morbidity and mortality. Here, we report the first identified <i>S. aureus</i> factor (lipase 1) that enhances IAV replication during infection via positive modulation of virus budding. The effect is observed <i>in vivo</i> in embryonated hen's eggs and greatly enhances the yield of a vaccine strain, a finding that could be applied to address global shortages of influenza vaccines.