Respiratory Syncytial Virus Protects Bystander Cells against Influenza A Virus Infection by Triggering Secretion of Type I and Type III Interferons
Maciej Czerkies, Marek Kochańczyk, Zbigniew Korwek, Wiktor Prus, Tomasz Lipniacki
Abstract
Influenza A virus (IAV) and respiratory syncytial virus (RSV) are common recurrent respiratory infectants that show a relatively high coincidence. We demonstrated that preinfection with RSV partitions the cell population into a subpopulation susceptible to subsequent infection with IAV and an IAV-proof subpopulation. The susceptible cells are those already compromised and efficiently expressing RSV, whereas the bystander cells are resistant to IAV infection. The cross-protective effect critically depends on IFN-β and IFN-λ signaling and thus ensues when the proportion of cells preinfected with RSV is relatively low yet sufficient to trigger a pervasive antiviral state in bystander cells. Our study suggests that mild, but not severe, respiratory infections may have a short-lasting protective role against more dangerous respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).