MOV10 inhibits SADS-CoV replication by enhancing TRIM24-mediated K63-linked TRAF3 ubiquitination, and this inhibition is antagonized by viral N protein
- 1State Key Laboratory of Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
Abstract
The global outbreak of SARS-CoV-2 has resulted in a renewed focus on coronaviruses with the potential for cross-species transmission and mutation risks. In particular, swine acute diarrhea syndrome coronavirus (SADS-CoV), potentially originating from the intermediate horseshoe bat (Rhinolophus affinis), is a novel coronavirus that causes acute diarrhea, vomiting, and high mortality in suckling piglets. Innate immunity plays a crucial role in defending the host against invading pathogens. Previous studies have identified several host factors that inhibit SADS-CoV replication through innate immunity; however, research on SADS-CoV remains insufficient compared to that on other coronaviruses. This study demonstrates that Moloney leukemia virus 10 protein (MOV10) exerts anti-SADS-CoV activity via its N-terminal domain in a helicase activity-independent manner. Mechanistic analysis reveals that MOV10 induces translocation of tripartite motif-containing 24 (TRIM24) from the nucleus to the cytoplasm. The cytoplasmically localized TRIM24 binds to MOV10 and TNF receptor-associated factor 3 (TRAF3) to form a ternary complex. Functional studies demonstrate that MOV10 strengthens the interaction between TRIM24 and TRAF3 in a dose-dependent manner and facilitates TRIM24-mediated K63-linked ubiquitination of TRAF3, thereby activating interferon immune responses. Furthermore, we identify the strategies by which SADS-CoV evades innate immunity. The viral N protein inhibits the antiviral effect of MOV10 by disrupting the interaction between MOV10 and TRAF3 and by promoting K48-linked polyubiquitination of TRAF3, leading to TRAF3 degradation via the ubiquitin-proteasome pathway. Collectively, our findings reveal the role of MOV10 in antiviral immunity and how SADS-CoV evades host immune defense.
IMPORTANCE: Moloney leukemia virus 10 protein (MOV10), a DExD-box RNA helicase, is a known component of cytoplasmic RNA processing centers known as P bodies. As an interferon-stimulated gene (ISG), MOV10 exhibits broad-spectrum antiviral activity against multiple viruses, including SARS-CoV-2, HIV, HSV-1, IAV, and PRRSV. Here, we identify a novel helicase-independent antiviral mechanism of MOV10 against SADS-CoV. In this study, we show that MOV10 bridges TRIM24 and TRAF3 and facilitates K63-linked ubiquitination of TRAF3 independent of its helicase activity. This process strongly amplifies downstream interferon antiviral responses and suppresses viral replication. Furthermore, the SADS-CoV N protein efficiently antagonizes MOV10-mediated immune defense by disrupting the MOV10-TRAF3 interaction and inducing K48-linked ubiquitination and proteasomal degradation of TRAF3. Collectively, this study establishes a previously uncharacterized MOV10-TRIM24-TRAF3 antiviral regulatory axis, which offers new mechanistic insights into how coronaviruses evade host immune defenses.
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BibTeX
@article{zeng2026mov10,
title = {{MOV10 inhibits SADS-CoV replication by enhancing TRIM24-mediated K63-linked TRAF3 ubiquitination, and this inhibition is antagonized by viral N protein}},
author = {Miaomiao Zeng and Dakai Liu and Jiyu Zhang and Liaoyuan Zhang and Hongyan Shi and Xin Zhang and Jianfei Chen and Xiuwen Li and Jialin Zhang and Tingshuai Feng and Xinwei Sun and Junyi Su and Zhaoyang Ji and Li Feng and Da Shi},
journal = {Journal of Virology},
year = {2026},
month = sep,
doi = {10.1128/jvi.01215-26},
url = {https://doi.org/10.1128/jvi.01215-26},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - MOV10 inhibits SADS-CoV replication by enhancing TRIM24-mediated K63-linked TRAF3 ubiquitination, and this inhibition is antagonized by viral N protein
AU - Miaomiao Zeng
AU - Dakai Liu
AU - Jiyu Zhang
AU - Liaoyuan Zhang
AU - Hongyan Shi
AU - Xin Zhang
AU - Jianfei Chen
AU - Xiuwen Li
AU - Jialin Zhang
AU - Tingshuai Feng
AU - Xinwei Sun
AU - Junyi Su
AU - Zhaoyang Ji
AU - Li Feng
AU - Da Shi
PY - 2026
DA - 2026/09/29
JO - Journal of Virology
DO - 10.1128/jvi.01215-26
UR - https://doi.org/10.1128/jvi.01215-26
AB - The global outbreak of SARS-CoV-2 has resulted in a renewed focus on coronaviruses with the potential for cross-species transmission and mutation risks. In particular, swine acute diarrhea syndrome coronavirus (SADS-CoV), potentially originating from the intermediate horseshoe bat (Rhinolophus affinis), is a novel coronavirus that causes acute diarrhea, vomiting, and high mortality in suckling piglets. Innate immunity plays a crucial role in defending the host against invading pathogens. Previous studies have identified several host factors that inhibit SADS-CoV replication through innate immunity; however, research on SADS-CoV remains insufficient compared to that on other coronaviruses. This study demonstrates that Moloney leukemia virus 10 protein (MOV10) exerts anti-SADS-CoV activity via its N-terminal domain in a helicase activity-independent manner. Mechanistic analysis reveals that MOV10 induces translocation of tripartite motif-containing 24 (TRIM24) from the nucleus to the cytoplasm. The cytoplasmically localized TRIM24 binds to MOV10 and TNF receptor-associated factor 3 (TRAF3) to form a ternary complex. Functional studies demonstrate that MOV10 strengthens the interaction between TRIM24 and TRAF3 in a dose-dependent manner and facilitates TRIM24-mediated K63-linked ubiquitination of TRAF3, thereby activating interferon immune responses. Furthermore, we identify the strategies by which SADS-CoV evades innate immunity. The viral N protein inhibits the antiviral effect of MOV10 by disrupting the interaction between MOV10 and TRAF3 and by promoting K48-linked polyubiquitination of TRAF3, leading to TRAF3 degradation via the ubiquitin-proteasome pathway. Collectively, our findings reveal the role of MOV10 in antiviral immunity and how SADS-CoV evades host immune defense. IMPORTANCE: Moloney leukemia virus 10 protein (MOV10), a DExD-box RNA helicase, is a known component of cytoplasmic RNA processing centers known as P bodies. As an interferon-stimulated gene (ISG), MOV10 exhibits broad-spectrum antiviral activity against multiple viruses, including SARS-CoV-2, HIV, HSV-1, IAV, and PRRSV. Here, we identify a novel helicase-independent antiviral mechanism of MOV10 against SADS-CoV. In this study, we show that MOV10 bridges TRIM24 and TRAF3 and facilitates K63-linked ubiquitination of TRAF3 independent of its helicase activity. This process strongly amplifies downstream interferon antiviral responses and suppresses viral replication. Furthermore, the SADS-CoV N protein efficiently antagonizes MOV10-mediated immune defense by disrupting the MOV10-TRAF3 interaction and inducing K48-linked ubiquitination and proteasomal degradation of TRAF3. Collectively, this study establishes a previously uncharacterized MOV10-TRIM24-TRAF3 antiviral regulatory axis, which offers new mechanistic insights into how coronaviruses evade host immune defenses.
SN - 0022-538X
SN - 1098-5514
ER -