DDX58 binds SARS-CoV-2 dsRNA intermediates

Stable Identifier
Reaction [binding]
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
SARS-CoV-2 dsRNA binds to RIG-I
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

The replication strategy of SARS-CoV-2 can generate double-stranded RNA (dsRNA) intermediates, that may act as pathogen-associated molecular patterns (PAMPs) recognized by cytoplasmic pattern recognition receptor (PRR) such as antiviral innate immune response receptor RIG-I (also known as DEAD box protein 58, DDX58). DDX58 recognizes short dsRNAs. Viral RNA binding provokes a change in DDX58 conformation exposing the caspase activation and recruitment domain (CARD) leading to DDX58 oligomerization, allowing it to interact with mitochondrial antiviral‑signaling protein (MAVS, IPS‑1).

Gene ablation using CRISPR/Cas9 showed that both DDX58 and IFIH1 sense severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection in human embryonic kidney HEK293T cells (Kouwaki T et al. 2021). Similar findings were reported for SARS-CoV-2-infected human adenocarcinoma-derived lung epithelial Calu-3 cells (Thorne LG et al. 2021). On the contrary, several studies showed that depletion of DDX58 had no effect in infected Calu-3 cells (Sampaio NG et al. 2021; Yin X et al. 2021; Rebendenne A et al. 2021). Another group reported that the helicase domain of DDX58 interacts with the 3′ UTR of the SARS-CoV-2 RNA in human lung epithelial cells, though this interaction failed to activate the ATPase activity of DDX58 and binding to MAVS (Yamada T et al. 2021). DDX58 (RIG-I), along with other proteins associated to virus infection (MAVS, TRAFs), were differentially expressed in COVID-19 patients vs healthy controls (Leng L et al. 2020). This Reactome event describes binding of DDX58 (RIG-I) to SARS-CoV-2 dsRNA intermediates, however the role of DDX58 in the antiviral innate immune response to SARS-CoV-2 remains elusive.

Literature References
PubMed ID Title Journal Year
15208624 The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses

Taira, K, Shinobu, N, Yoneyama, M, Fujita, T, Miyagishi, M, Kikuchi, M, Imaizumi, T, Natsukawa, T

Nat Immunol 2004
This event is regulated
Cite Us!