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

Haney, Joanne; Vijayakrishnan, Swetha; Streetley, James; Dee, Kieran; Goldfarb, Daniel Max; Clarke, Mairi; Mullin, Margaret; Carter, Stephen D; Bhella, David; Murcia, Pablo R

Interactions between co-circulating respiratory viruses are recognized for their impact on viral transmission and clinical outcomes. However, the consequences of these virus-virus interactions at the cellular level are unclear. We coinfected human lung cells with influenza A virus (IAV) and respiratory syncytial virus (RSV). Super-resolution microscopy combined with live-cell imaging and scanning electron microscopy identified extracellular and membrane-associated filamentous structures, likely composed of elements of both IAV and RSV virions. Cryo-electron tomography confirmed the presence of chimeric virus particles exhibiting glycoproteins and ribonucleoproteins of both parental viruses. Functional assays revealed chimeric particles facilitate IAV infection in cells depleted of IAV receptors, demonstrating expanded tropism. Our observations define a previously unknown interaction that is likely to affect virus pathogenesis and have profound implications for infection biology.