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

Fritzlar, S.; Lakdawala, S.; Roberts, J. A.; Coin, L. J. M.; Deng, Y.-M.; Moselen, J.; Le Sage, V.; Mackenzie, J.; Labzin, L.; Brooks, A. G.; Reading, P.; Londrigan, S.

doi:10.1101/2023.12.04.570004

bioRxiv · 10.1101/2023.12.04.570004

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

Fritzlar, S.·Lakdawala, S.·Roberts, J. A.·Coin, L. J. M.·Deng, Y.-M.·Moselen, J.·Le Sage, V.·Mackenzie, J.·Labzin, L.·Brooks, A. G.·Reading, P.·Londrigan, S.

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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.

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Fritzlar, S., Lakdawala, S., Roberts, J. A., Coin, L. J. M., Deng, Y.-M., Moselen, J., Le Sage, V., Mackenzie, J., Labzin, L., Brooks, A. G., Reading, P., Londrigan, S.. 2023-12-05. Influenza infected macrophages release viral ribonucleoproteins that shape the local host response. https://doi.org/10.1101/2023.12.04.570004

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