Home HOME Acta Virologica 2022 Acta Virologica Vol.66, No.3, p. 263 – 274, 2022

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Founded: 1957
ISSN 0001-723X
E-ISSN 1336-2305

Published in English

Impact Factor = 1.82

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Acta Virologica Vol.66, No.3, p. 263 – 274, 2022

Title: Generation and characterization of interferon-beta-resistant H1N1 influenza A virus
Author: Brady T. Hickerson, Simone E. Adams, Nicolai V. Bovin, Raymond P. Donnelly, Natalia A. Ilyushina

Abstract: Interferons (IFNs) mediate innate antiviral activity against many types of viruses, including influenza viruses. In light of their potential use as anti-influenza agents, we examined whether resistance to these host antiviral proteins can develop. We generated IFN-β-resistant variants of the A/California/04/09 (H1N1) virus by serial passage in a human airway epithelial cell line, Calu-3, under IFN-β selective pressure. The combination of specific mutations (i.e., L373I in PB1, K154E1, D222G1, I56V2, and V122I2 in HA, and M269I in NA) correlated with decreased ability of the virus to induce expression of IFN (IFNB1, IFNL1, and IFNL2/3) and IFN-stimulated genes (IFIT1, IFIT3, OAS1, IRF7, and MX1) by target respiratory epithelial cells. In addition, the IFN-induced mutations were associated with decreased HA binding affinity to α2,6 sialyl receptors, reduced NA enzyme catalytic activity, and decreased polymerase transcription activity. Our findings demonstrate that the mutations in the influenza HA, NA, and PB1 proteins induced by IFN-b selective pressure significantly increase viral ability to productively infect and replicate in host cells.

Keywords: influenza A virus; interferon-β; lung epithelial cells; interferon response
Published online: 27-Aug-2022
Year: 2022, Volume: 66, Issue: 3 Page From: 263, Page To: 274

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