Coronavirus nucleocapsid proteins differentially antagonize RIG-I-like receptor signaling to shape pathogenicity
- 1Zhejiang University
Abstract
Coronaviruses cause human infections with divergent clinical outcomes. Viral proteins likely play important roles in the severity of human diseases but are poorly defined. In this study, we discovered that viral nucleocapsid (N) proteins from various human coronaviruses have distinct abilities to antagonize human innate immune responses. N proteins from more pathogenic coronaviruses, such as SARS-CoV and SARS-CoV-2, have more potent activities specifically against human RIG-I-like receptor (RLR) activation than less pathogenic coronaviruses including OC43 and HKU1. Mechanistically, the SARS-CoV-2 N protein interacts with RLR pathway viral RNA sensors MDA5 and RIG-I and inhibits their interaction with MAVS. The CTD of SARS-CoV-2 N protein is an important region for RLR antagonism. Consequently, N proteins from more pathogenic coronaviruses promote viral replication more effectively than N proteins from less pathogenic coronaviruses. Blocking N protein function may be a promising antiviral strategy.
Related
- A nucleocapsid-tagged fluorescent pangolin coronavirus enables authentic-virus neutralization assays and localizes the antiviral activity of cepharanthine to viral entry
- The biochemical composition of coronavirus Nucleocapsid proteins drives the bicistronic properties of their sub-genomic mRNAs
- A feline coronavirus nucleocapsid protein disrupts ZC3HAV1–viral RNA association to counteract host RNA-level restriction
- LIF-LIFR/gp130 Survival Signaling and Connexin 47 Dysregulation upon Murine-β-Coronavirus Infection: Discovery of a Novel ERK2 Phosphorylation Site at Cx47 C-Terminal Domain
- Host soluble inositol phosphate signaling promotes coronavirus replication
BibTeX
@misc{rui2026coronavirus,
title = {{Coronavirus nucleocapsid proteins differentially antagonize RIG-I-like receptor signaling to shape pathogenicity}},
author = {Y. Rui and Y. Wang and S. Chen and Y. Cao and Y. Hu and S. Shen and Q. Ding and J. Su and X.-F. Yu},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.09.758129},
url = {https://www.biorxiv.org/content/10.64898/2026.10.09.758129v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Coronavirus nucleocapsid proteins differentially antagonize RIG-I-like receptor signaling to shape pathogenicity
AU - Y. Rui
AU - Y. Wang
AU - S. Chen
AU - Y. Cao
AU - Y. Hu
AU - S. Shen
AU - Q. Ding
AU - J. Su
AU - X.-F. Yu
PY - 2026
DA - 2026/10/09
PB - bioRxiv
DO - 10.64898/2026.10.09.758129
UR - https://www.biorxiv.org/content/10.64898/2026.10.09.758129v1
AB - Coronaviruses cause human infections with divergent clinical outcomes. Viral proteins likely play important roles in the severity of human diseases but are poorly defined. In this study, we discovered that viral nucleocapsid (N) proteins from various human coronaviruses have distinct abilities to antagonize human innate immune responses. N proteins from more pathogenic coronaviruses, such as SARS-CoV and SARS-CoV-2, have more potent activities specifically against human RIG-I-like receptor (RLR) activation than less pathogenic coronaviruses including OC43 and HKU1. Mechanistically, the SARS-CoV-2 N protein interacts with RLR pathway viral RNA sensors MDA5 and RIG-I and inhibits their interaction with MAVS. The CTD of SARS-CoV-2 N protein is an important region for RLR antagonism. Consequently, N proteins from more pathogenic coronaviruses promote viral replication more effectively than N proteins from less pathogenic coronaviruses. Blocking N protein function may be a promising antiviral strategy.
ER -