Journal Article

Broad-Spectrum Antiviral Activity of Influenza A Defective Interfering Particles against Respiratory Syncytial, Yellow Fever, and Zika Virus Replication In Vitro

Marsall, Patrick, Hein, Marc Dominique, Kupke, Sascha Young, Wynserski, Nancy, Marichal-Gallardo, Pavel, Pelz, Lars, Reichl, Udo, Piagnani, Elena

2023

Overview

New broadly acting and readily available antiviral agents are needed to combat existing and emerging viruses. Defective interfering particles (DIPs) of influenza A virus (IAV) are regarded as promising options for the prevention and treatment of IAV infections. Interestingly, IAV DIPs also inhibit unrelated viral infections by stimulating antiviral innate immunity. Here, we tested the ability of IAV DIPs to suppress respiratory syncytial, yellow fever and Zika virus infections in vitro. In human lung (A549) cells, IAV DIP co-infection inhibited the replication and spread of all three viruses. In contrast, we observed no antiviral activity in Vero cells, which are deficient in the production of interferon (IFN), demonstrating its importance for the antiviral effect. Further, in A549 cells, we observed an enhanced type-I and type-III IFN response upon co-infection that appears to explain the antiviral potential of IAV DIPs. Finally, a lack of antiviral activity in the presence of the Janus kinase 1/2 (JAK1/2) inhibitor ruxolitinib was detected. This revealed a dependency of the antiviral activity on the JAK/signal transducers and activators of transcription (STAT) signaling pathway. Overall, this study supports the notion that IAV DIPs may be used as broad-spectrum antivirals to treat infections with a variety of IFN-sensitive viruses, particularly respiratory viruses.

• Publisher: MDPI AG,MDPI
• Subject: Antiviral activity / Antiviral agents / Antiviral drugs / antiviral properties / broad-spectrum antiviral / Care and treatment / Cell culture / Complications and side effects / defective interfering particles / Dengue fever / Diagnosis / humans / Infections / Influenza / Influenza A / Influenza A virus / Inhibitor drugs / Innate immunity / Interferon / interferons / Janus kinase / lungs / mixed infection / non-specific protein-tyrosine kinase / Older people / Patient outcomes / Propagation / Proteins / Replication / Respiratory syncytial virus / Severe acute respiratory syndrome coronavirus 2 / Signal transduction / Sodium / Transcription factors / Vaccines / Vero cells / Viral infections / virus replication / Viruses / West Nile virus / Yellow fever / yellow fever virus / Zika virus