In a world first, scientists have witnessed the fusion two viruses, influenza A virus (IAV) and respiratory syncytial virus (RSV), forming a single, hybrid virus particle (HVP). The discovery was published in Nature Microbiology.
Viruses often share tropism for the same system, such as respiratory viruses preferentially infecting the respiratory system. Coinfections by more than one virus represent between ~10–30% of all respiratory viral infections and are common among children. The clinical impact of viral coinfections is unclear: while some studies indicate that coinfections do not alter the outcome of disease, others report increased incidence of viral pneumonia.
Though evidence suggests virus–virus interactions play an important role in virus dynamics and transmission, viruses are typically studied in isolation. Recent work showed that interactions among respiratory viruses occur and have impacts at multiple levels, from populations, to individuals and tissues. However, studies characterising direct virus–virus interactions within cells are scarce. Here we report previously unknown interactions between IAV and RSV, two clinically important respiratory viruses that belong to different taxonomical families.
To investigate virus–virus interactions, the researchers infected human lung cells with both influenza A virus (IAV) and respiratory syncytial virus (RSV). Using super-resolution microscopy, live-cell imaging, scanning electron microscopy and cryo-electron tomography, the researchers found extracellular and membrane-associated filamentous structures consistent with hybrid viral particles (HVPs).
The researchers found that HVPs harbour surface glycoproteins and ribonucleoproteins of IAV and RSV. HVPs use the RSV fusion glycoprotein to evade anti-IAV neutralising 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 latching on together 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,” the researchers wrote.
“This kind of hybrid virus has never been described before,” virologist and senior author Pablo Murcia told The Guardian. “We are talking about viruses from two completely different families combining together with the genomes and the external proteins of both viruses. It is a new type of virus pathogen.”
When IAV and RSV coinfect, IAV becomes more infectious, infecting a wider array of human cells. Carrying the RSV surface proteins, IAV was able to better evade the immune system. The HVP also spread into cells lacking influenza receptors, letting it progress further down the respiratory tract.
The relationship is not mutually beneficial for the viruses as RSV loses potency. Overall though, pilfering another virus’s tools could play a role in viral pneumonia.
“RSV tends to go lower down into the lung than the seasonal flu virus, and you’re more likely to get more severe disease the further down the infection goes,” said Dr Stephen Griffin, a virologist at the University of Leeds who was not involved in the study.
“It is another reason to avoid getting infected with multiple viruses, because this [hybridisation] is likely to happen all the more if we don’t take precautions to protect our health,” he added.
The researchers also found that the combination of viruses was important; IAV did not form an effective hybrid with rhinovirus.
