Influenza infected macrophages release viral ribonucleoproteins that shape the local host response

Abstract

Airway epithelial cells and macrophages (M{Phi}) represent cellular targets of infection by influenza A virus (IAV). Epithelial cells support IAV infection and replication by enabling the generation and release of new viral particles (productive replication). In contrast, M{Phi} are susceptible to initial IAV infection but the release of infectious viral particles is inhibited through abortive replication. Despite the lack of infectious virions released from infected M{Phi}, we detected newly synthesised viral RNA and nucleoprotein (NP) in M{Phi} supernatants. We show that viral RNA is released from infected M{Phi} as viral ribonucleoprotein (vRNP) complexes which elicits potent inflammatory responses when exposed to uninfected cells. These vRNPs specifically induced IL-1{beta}, CXCL13, IL-32, CCL4 and CXCL10 in uninfected cells and were at least partially sensed through the RIG-I/MDA5 pathway. While M{Phi} represent a dead-end for IAV infection through abortive replication, the release of vRNPs shapes immune repsonses of uninfected cells in the local microenvironment.