In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 19, No. 8 ( 2023-8-21), p. e1011577-
Abstract:
Circular RNAs (circRNAs) are involved in various biological roles, including viral infection and antiviral immune responses. To identify influenza A virus (IAV) infection-related circRNAs, we compared the circRNA profiles of A549 cells upon IAV infection. We found that circVAMP3 is substantially upregulated after IAV infection or interferon (IFN) stimulation. Furthermore, IAV and IFN-β induced the expression of QKI-5, which promoted the biogenesis of circVAMP3 . Overexpression of circVAMP3 inhibited IAV replication, while circVAMP3 knockdown promoted viral replication, suggesting that circVAMP3 restricts IAV replication. We verified the effect of circVAMP3 on viral infection in mice and found that circVAMP3 restricted IAV replication and pathogenesis in vivo . We also found that circVAMP3 functions as a decoy to the viral proteins nucleoprotein (NP) and nonstructural protein 1 (NS1). Mechanistically, circVAMP3 interfered with viral ribonucleoprotein complex activity by reducing the interaction of NP with polymerase basic 1, polymerase basic 2, or vRNA and restored the activation of IFN-β by alleviating the inhibitory effect of NS1 to RIG-I or TRIM25. Our study provides new insights into the roles of circRNAs, both in directly inhibiting virus replication and in restoring innate immunity against IAV infection.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1011577
DOI:
10.1371/journal.ppat.1011577.g001
DOI:
10.1371/journal.ppat.1011577.g002
DOI:
10.1371/journal.ppat.1011577.g003
DOI:
10.1371/journal.ppat.1011577.g004
DOI:
10.1371/journal.ppat.1011577.g005
DOI:
10.1371/journal.ppat.1011577.g006
DOI:
10.1371/journal.ppat.1011577.g007
DOI:
10.1371/journal.ppat.1011577.g008
DOI:
10.1371/journal.ppat.1011577.s001
DOI:
10.1371/journal.ppat.1011577.s002
DOI:
10.1371/journal.ppat.1011577.s003
DOI:
10.1371/journal.ppat.1011577.s004
DOI:
10.1371/journal.ppat.1011577.s005
DOI:
10.1371/journal.ppat.1011577.s006
DOI:
10.1371/journal.ppat.1011577.s007
DOI:
10.1371/journal.ppat.1011577.s008
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2205412-1
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