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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:15

Enthalten in:

Viruses - 15(2023), 9 vom: 04. Sept.

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext

Themen:

2215-21-6
3,5-diisopropylsalicylic acid
Antiviral Agents
Broad-spectrum antiviral
Defective interfering particles
Journal Article
Respiratory syncytial virus
Yellow fever virus
Zika virus

Anmerkungen:

Date Completed 04.10.2023

Date Revised 06.10.2023

published: Electronic

Citation Status MEDLINE

doi:

10.3390/v15091872

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM362625433