In a first, scientists observed a hybrid virus that evades immune system

In their laboratory-based research on human lung cell samples, researchers found that coinfection with influenza A and RSV could lead to the emergence of two new hybrid virus particles, with the potential to bypass immunity. They also used super-resolution microscopy, live-cell imaging, and cryo-electron tomography (Cryo-ET) to see the hybrid virus particles that contain genetic information from both influenza A and RSV. And using the entry mechanism from the RSV virus, one of the hybrid virus particles managed to infect new cells with influenza A and enabled them to evade the immune response.

Researchers think the new findings give insight into previously unknown interactions between respiratory viruses. The interactions could help scientists understand why some patients coinfected with more than one virus experience more severe effects and require more complicated medical care.

"This was an unexpected but very exciting discovery that challenges what we know about how viral particles are formed within a cell. Our next steps are to find out if hybrid particles are formed in patients with coinfections, and to identify which virus combinations can generate hybrid particles, although our working assumption is that only few respiratory viruses will form hybrid viruses," said Professor Pablo Murcia from the MRC-University of Glasgow Centre for Virus Research.

More research on the virus coinfection is needed

Despite mounting evidence that interactions among viruses have a significant impact on virus dynamics and transmission, the majority of what scientists know about the biology of viruses is based on studying each virus separately.

Therefore, the new study is significant for suggesting that more research on the virus coinfection process is needed.

"Respiratory viruses exist as part of a community of many viruses that all target the same region of the body, like an ecological niche. We need to understand how these infections occur within the context of one another to gain a fuller picture of the biology of each individual virus. Coinfection studies can help us in preparing for future pandemics by understanding how the introduction of one virus can influence and interact with other circulating viruses," said Dr Joanne Haney, the first author of the paper, from the MRC-University of Glasgow Centre for Virus Research.

The study paper was published in Nature Microbiology.

Abstract:

Interactions between respiratory viruses during infection affect 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 found that HVPs harbour surface glycoproteins and ribonucleoproteins of IAV and RSV. HVPs use the RSV fusion glycoprotein to evade anti-IAV neutralizing antibodies and infect and spread among cells lacking IAV receptors. Finally, we show that IAV and RSV coinfection in primary cells of the bronchial epithelium results in viral proteins from both viruses co-localizing at the apical cell surface. Our observations define a previously unknown interaction between respiratory viruses that might affect virus pathogenesis by expanding virus tropism and enabling immune evasion.