E3 ubiquitin ligase MARCH5 positively regulates Japanese encephalitis virus infection by catalyzing the K27-linked polyubiquitination of viral E protein and inhibiting MAVS-mediated type I interferon production DOI Creative Commons
Chenxi Li,

Chenyang Tang,

Xiqian Liu

et al.

mBio, Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

ABSTRACT Membrane-associated RING-CH-type finger (MARCH) proteins, a class of E3 ubiquitin ligases, have been reported to be involved in the infection multiple viruses and regulation type I interferon (IFN) production. However, specific role mechanisms by which MARCH proteins influence Japanese encephalitis virus (JEV) remain poorly understood. Here, we systematically investigate functional relevance JEV replication examining effects siRNA-mediated knockdown MARCHs on viral infection. We identified MARCH5 as positive regulator replication. The knockout dramatically reduced yields, whereas its overexpression significantly enhanced Mechanistically, specifically interacts with envelope (E) protein promotes K27-linked polyubiquitination at lysine (K) residues 136 166. This ubiquitination enhances attachment permissive cells. Substituting these arginine (R) attenuated vitro virulence vivo . Furthermore, upregulated expression MARCH5. also discovered that degrades mitochondrial antiviral-signaling (MAVS) through ubiquitin-proteasome pathway catalyzing K48-linked ubiquitination, thereby inhibiting IFN production JEV-infected suppression further facilitates In conclusion, findings disclosed novel positively regulating revealed an important mechanism employed regulate innate immune response. IMPORTANCE is leading cause many countries Asia estimated 100,000 clinical human cases causes economic loss swine industry. Until now, there no clinically approved antiviral for treatment Although vaccination prophylaxis widely regarded most effective strategy preventing (JE), incidence JE continues rise. Thus, deeper understanding virus-host interaction will enrich our knowledge underlying identify targets development next-generation live-attenuated vaccines therapies. To best knowledge, this study first pro-viral host factor elucidated two distinct First, E mediates K136 K166 facilitate efficient attachment. double mutations K136R-K166R mice. Second, induced suppresses RIG-I-like receptor (RLR) signaling benefit downregulates conjugating polyubiquitin K286 MAVS, leads MAVS degradation pathway. summary, provides insights into played identifies sites could targeted attenuation therapeutics.

Language: Английский

The full-length nsp2 replicase contributes to viral assembly in highly pathogenic PRRSV-2 DOI Creative Commons

Yuan-Zhe Bai,

Shujie Wang, Yue Sun

et al.

Journal of Virology, Journal Year: 2024, Volume and Issue: 99(1)

Published: Nov. 27, 2024

Porcine reproductive and respiratory syndrome viruses (PRRSVs) are significant pathogens that affect the global swine industry. Its virions consist of a central core composed nucleocapsid (N) protein, surrounded by multiple distinct viral envelope proteins. However, mechanisms underlying recognition packaging N protein proteins remain elusive. In this study, we elucidated role nonstructural 2 (nsp2) from highly pathogenic PRRSV-2 (HP-PRRSV-2) in assembly. Firstly, among all tested proteins, only glycoprotein 5 (GP5) exhibits limited interaction with protein. Interestingly, demonstrated full-length nsp2 co-immunoprecipitates (Co-IPs) presence nsp2, interacts Moreover, upon infection, Co-IP experiments using nsp2-specific antibodies or N-specific revealed formation complex between M GP2a, GP5. neither two short forms nsp2-namely nsp2TF nor nsp2N-participates process as they fail to interact Finally, our results demonstrate occurs endoplasmic reticulum (ER) ER-Golgi intermediate compartment (ERGIC). Overall, findings unveil novel functional for HP-PRRSV-2 facilitating assembly proteins.IMPORTANCEThe virus arteriviruses remains largely elusive, including direct potential requirement additional where assembles during lifecycle unclear. This study reveals porcine type (HP-PRRSV-2), highlighting its involvement These provide crucial insights into enhance understanding their lifecycle. offers an alternative approach developing new antiviral strategy targeting

Language: Английский

Citations

6
MARCH8 ubiquitinates and degrades CEMIP to induce colorectal cancer cell ferroptosis through inactivating PI3K/AKT pathway DOI
Lintao Liu, Cheng Zhang, Bo Yang

et al.

Pathology - Research and Practice, Journal Year: 2025, Volume and Issue: 269, P. 155909 - 155909

Published: March 11, 2025

Language: Английский

Citations

0
E3 ubiquitin ligase MARCH5 positively regulates Japanese encephalitis virus infection by catalyzing the K27-linked polyubiquitination of viral E protein and inhibiting MAVS-mediated type I interferon production DOI Creative Commons
Chenxi Li,

Chenyang Tang,

Xiqian Liu

et al.

mBio, Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

ABSTRACT Membrane-associated RING-CH-type finger (MARCH) proteins, a class of E3 ubiquitin ligases, have been reported to be involved in the infection multiple viruses and regulation type I interferon (IFN) production. However, specific role mechanisms by which MARCH proteins influence Japanese encephalitis virus (JEV) remain poorly understood. Here, we systematically investigate functional relevance JEV replication examining effects siRNA-mediated knockdown MARCHs on viral infection. We identified MARCH5 as positive regulator replication. The knockout dramatically reduced yields, whereas its overexpression significantly enhanced Mechanistically, specifically interacts with envelope (E) protein promotes K27-linked polyubiquitination at lysine (K) residues 136 166. This ubiquitination enhances attachment permissive cells. Substituting these arginine (R) attenuated vitro virulence vivo . Furthermore, upregulated expression MARCH5. also discovered that degrades mitochondrial antiviral-signaling (MAVS) through ubiquitin-proteasome pathway catalyzing K48-linked ubiquitination, thereby inhibiting IFN production JEV-infected suppression further facilitates In conclusion, findings disclosed novel positively regulating revealed an important mechanism employed regulate innate immune response. IMPORTANCE is leading cause many countries Asia estimated 100,000 clinical human cases causes economic loss swine industry. Until now, there no clinically approved antiviral for treatment Although vaccination prophylaxis widely regarded most effective strategy preventing (JE), incidence JE continues rise. Thus, deeper understanding virus-host interaction will enrich our knowledge underlying identify targets development next-generation live-attenuated vaccines therapies. To best knowledge, this study first pro-viral host factor elucidated two distinct First, E mediates K136 K166 facilitate efficient attachment. double mutations K136R-K166R mice. Second, induced suppresses RIG-I-like receptor (RLR) signaling benefit downregulates conjugating polyubiquitin K286 MAVS, leads MAVS degradation pathway. summary, provides insights into played identifies sites could targeted attenuation therapeutics.

Language: Английский

Citations

0