Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 80, Issue 12, Pages -Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-023-05011-3
Keywords
SARS-CoV-2; Type-I IFN; ORF6; RIG-I; TRIM25; Ubiquitination
Categories
Ask authors/readers for more resources
Evasion and antagonism of host cellular immunity provide replication advantage to SARS-CoV-2. ORF6 protein was found to mitigate type-I interferon induction and signaling. ORF6 directly interacts with RIG-I and reduces K63-linked ubiquitinated RIG-I, blocking downstream type-I interferon induction and signaling. These findings contribute to understanding how SARS-CoV-2 evades the host immune response.
Evasion and antagonism of host cellular immunity upon SARS-CoV-2 infection provide replication advantage to the virus and contribute to COVID-19 pathogenesis. We explored the ability of different SARS-CoV-2 proteins to antagonize the host's innate immune system and found that the ORF6 protein mitigated type-I Interferon (IFN) induction and downstream IFN signaling. Our findings also corroborated previous reports that ORF6 blocks the nuclear import of IRF3 and STAT1 to inhibit IFN induction and signaling. Here we show that ORF6 directly interacts with RIG-I and blocks downstream type-I IFN induction and signaling by reducing the levels of K63-linked ubiquitinated RIG-I. This involves ORF6-mediated targeting of E3 ligase TRIM25 for proteasomal degradation, which was also observed during SARS-CoV-2 infection. The type-I IFN antagonistic activity of ORF6 was mapped to its C-terminal cytoplasmic tail, specifically to amino acid residues 52-61. Overall, we provide new insights into how SARS-CoV-2 inhibits type-I IFN induction and signaling through distinct actions of the viral ORF6 protein.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available