Generation of chimeric respiratory viruses with altered tropism by coinfection of influenza A virus and respiratory syncytial virus

Interactions between respiratory viruses impact viral transmission dynamics and clinical outcomes. To identify and characterize virus-virus interactions at the cellular level, we coinfected human lung cells with influenza A virus (IAV) and respiratory syncytial virus (RSV). Super-resolution microscopy, live-cell imaging, scanning electron microscopy, and cryo-electron tomography revealed extracellular and membrane-associated filamentous structures consistent with hybrid viral particles (HVPs). We show that HVPs harbor surface glycoproteins and ribonucleoproteins of IAV and RSV, and use the RSV fusion glycoprotein to evade anti-IAV neutralising antibodies and to infect and spread among cells lacking IAV receptors. Finally, we show evidence of IAV and RSV coinfection within cells of the bronchial epithelium, with viral proteins from both viruses co-localising at the apical surface. Our observations have profound implications for infection biology as they define a previously unknown interaction between respiratory viruses that might affect virus pathogenesis by expanding virus tropism and facilitating immune evasion.