In one of the largest, longest, and most comprehensive studies of respiratory virus infections in humans, Murcia and colleagues used a PCR assay that can identify members of 11 viral families to probe nasal and throat samples from more than 36,000 individuals who sought care from the National Health Service in Glasgow over 9 years. Among other examples of viral interference, their data clearly showed rhinovirus and influenza A peaked at different times demonstrating a “negative interaction” between the two viruses, the group concluded in the 26 December 2019 issue of the Proceedings of the National Academy of Sciences.
The next year, Foxman and colleagues reported finding interference after PCR testing for 10 different viruses in 13,000 respiratory samples from adults who sought care at the Yale New Haven hospital system. Between 2016 and 2019, about 7% of people tested positive for rhinovirus or influenza A virus, but of these 1911 samples, only 12 had both viruses, significantly fewer than expected, they reported in The Lancet Microbe. “It was great to see Ellen Foxman’s paper,” Murcia says. “She essentially showed similar results to ours, and they are completely independent studies.”
In the same report, Foxman pinned down the causal role of interferons. Like normal airways, the organoids her team makes from bronchial epithelial cells mount immune responses, including secreting interferons. Infecting organoids with rhinovirus nearly halted the growth of influenza A viruses added later. The rhinovirus infections led to the expression of a flood of interferon-related genes, the study showed. And when her team treated the organoids with drugs that blocked their cells from mounting an interferon response, the influenza viruses thrived.
Now, viral interference researchers are closely watching the newest respiratory virus to circle the globe. “What interactions could SARS-CoV-2 have with other viruses?” Murcia asks. “To this day, there are no robust epidemiological data.” For one thing, the widespread social distancing and mask wearing in many countries meant there was little chance to see interference in action. “There was almost no circulation of other respiratory viruses during the first 3 years of the pandemic,” Boivin says. Also, SARS-CoV-2 has many defences against interferons, including preventing their production, which might affect its interactions with other viruses.
Still, Foxman has published evidence that, in her organoid model, rhinovirus can interfere with SARS-CoV-2. And Boivin’s team has reported that influenza A and SARS-CoV-2 each can block the other in cell studies.
