Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by RIG-I
By Michaela U. Gack, Randy A. Albrecht, T. Urano, Kyung-Soo Inn, I-Chueh Huang, Elena Carnero, M. Farzan, S. Inoue, Jae U. Jung, A. García‐Sastre. Cell Host and Microbe, 2009
883 citations recorded by the source corpus.
SUMMARY TRIM25 mediates Lys 63-linked ubiquitination of the N-terminal CARDs of the viral RNA sensor RIG-I, leading to type I interferon (IFN) production. Here, we report that the influenza A virus non-structural protein 1 (NS1) specifically inhibits TRIM25-mediated RIG-I CARD ubiquitination, thereby suppressing RIG-I signal transduction. A novel domain in NS1 comprising E96/E97 residues mediates its interaction with the coiled-coil domain of TRIM25, thus blocking TRIM25 multimerization and RIG-I CARD ubiquitination. Furthermore, a recombinant influenza A virus expressing an E96A/E97A NS1 mutant is defective in blocking TRIM25-mediated anti-viral IFN response and loses virulence in mice. Our findings reveal a novel mechanism of influenza virus to inhibit host IFN response and also emphasize the vital role of TRIM25 in modulating viral infections.
Subfields: Epidemiology, Immunology
View Paper: https://www.semanticscholar.org/paper/6d39c620ae53f58b01693cc121a112f74ba3c68a
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In Epidemiology
In Immunology
- A. García‐Sastre
- V. Hornung
- Charles M. Rice
- J. Rehwinkel
- C. Reis e Sousa
- D. Goubau
- Shizuo Akira
- Jacques Banchereau
Citations in the corpus
- ATP-dependent effector-like functions of RIG-I like receptors (2015, background): “In contrast to MDA5, RIG-I was suppressed by NS1/E3L through an RNA-independent mechanism (Gack et al., 2009) (Figure 3B), and the suppression was not relieved by either RIG-IDN or MDA5DN (Figures 3E and S3D).”
- Influenza A viruses: new research developments (2011, background): “121 ), which is an antagonist of the IFN-mediated antiviral host respons”
- RIG-I detects viral genomic RNA during negative-strand RNA virus infection. (2010, background): “This model does not exclude additional modes of NS1 action, such as inhibition of TRIM25-mediated RIG-I ubiquitination (Gack et al., 2009).”
- Interferon-Stimulated Genes: A Complex Web of Host Defenses (2014, background): “In addition to STING, the mitochondrial antiviral-signaling protein (MAVS, also known as VISA, IPS-1, or Cardif) (86–88) is also found in this membrane-rich region, where it interacts with the RLRs RIG-I and MDA5 to further propagate innate immune signaling (Figure 2).”