Cullin 3-mediated ubiquitination restricts enterovirus D68 replication and is counteracted by viral protease 3C DOI Creative Commons
Yan Li,

Limei Qu,

Yubin Tang

и другие.

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Май 21, 2025

ABSTRACT Enterovirus D68 (EV-D68) has emerged as a significant threat to public health because of its association with respiratory illnesses and neurological complications, including acute flaccid myelitis. However, the molecular mechanisms underlying EV-D68 replication pathogenesis remain unclear. Here, we revealed novel interaction between host Cullin-RING E3 ligase system, specifically Cullin 3, which was reported restrict viral replication. We initially demonstrated that proteasome inhibition enhanced replication, suggesting an important role for ubiquitin–proteasome system in restriction. 3 further identified key factor inhibits downregulation expression increased titers. Mechanistically, observed target capsid protein VP1 ubiquitination degradation. determined utilize protease 3C cleave at Q681 residue, thereby inhibiting activity facilitating resistance 3-mediated This study uncovered host–virus arms race, wherein actively targets proteins degradation, proteases counteract this defense mechanism. Accordingly, these findings could lead more effective antiviral treatments. IMPORTANCE The (UPS) is critical cellular pathway involved regulation stability been implicated infections. infection not extensively explored. Our proves UPS, through scaffold can representing previously unrecognized Furthermore, describe strategy used evade mechanism comprising cleavage, broad implications understanding virus–host interactions inform development therapeutic strategies against other enteroviruses.

Язык: Английский

Initiator cell death event induced by SARS-CoV-2 in the human airway epithelium DOI Open Access
Kaixin Liang, Katherine C. Barnett, Martin Hsu

и другие.

Science Immunology, Год журнала: 2024, Номер 9(97)

Опубликована: Июль 12, 2024

Virus-induced cell death is a key contributor to COVID-19 pathology. Cell induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) well studied in myeloid cells but less its primary host type, angiotensin-converting enzyme (ACE2)–expressing human airway epithelia (HAE). SARS-CoV-2 induces apoptosis, necroptosis, and pyroptosis HAE organotypic cultures. Single-cell limiting-dilution analysis revealed that necroptosis the event infected cells, whereas uninfected bystanders undergo occurs later during infection. Mechanistically, viral Z-RNA binding Z-DNA–binding protein 1 (ZBP1) lung tissues from patients with COVID-19. The Delta (B.1.617.2) variant, which causes more disease than Omicron (B1.1.529) humans, associated orders of magnitude–greater Z-RNA/ZBP1 interactions, severity animal models. Thus, robust ZBP1-mediated severity.

Язык: Английский

Процитировано

11
Exploring enterovirus pathogenesis and cancer therapy potential through reverse genetics DOI Creative Commons
Shijin Wang, Qinghua Yu,

Zhou Junfeng

и другие.

Biosafety and Health, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

1
The SARS-CoV-2 3CL protease inhibits pyroptosis through the cleavage of gasdermin D DOI Creative Commons
Yecheng Zhang, Xiaotong Ji, Dan Huang

и другие.

Virologica Sinica, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
The underlying mechanism of Porcine Teschovirus 2 3Cpro antagonizing the NLRP3 inflammasome DOI

Xin-yu Zhang,

Yuying Li, Wei J. Chen

и другие.

Veterinary Microbiology, Год журнала: 2025, Номер unknown, С. 110479 - 110479

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Cullin 3-mediated ubiquitination restricts enterovirus D68 replication and is counteracted by viral protease 3C DOI Creative Commons
Yan Li,

Limei Qu,

Yubin Tang

и другие.

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Май 21, 2025

ABSTRACT Enterovirus D68 (EV-D68) has emerged as a significant threat to public health because of its association with respiratory illnesses and neurological complications, including acute flaccid myelitis. However, the molecular mechanisms underlying EV-D68 replication pathogenesis remain unclear. Here, we revealed novel interaction between host Cullin-RING E3 ligase system, specifically Cullin 3, which was reported restrict viral replication. We initially demonstrated that proteasome inhibition enhanced replication, suggesting an important role for ubiquitin–proteasome system in restriction. 3 further identified key factor inhibits downregulation expression increased titers. Mechanistically, observed target capsid protein VP1 ubiquitination degradation. determined utilize protease 3C cleave at Q681 residue, thereby inhibiting activity facilitating resistance 3-mediated This study uncovered host–virus arms race, wherein actively targets proteins degradation, proteases counteract this defense mechanism. Accordingly, these findings could lead more effective antiviral treatments. IMPORTANCE The (UPS) is critical cellular pathway involved regulation stability been implicated infections. infection not extensively explored. Our proves UPS, through scaffold can representing previously unrecognized Furthermore, describe strategy used evade mechanism comprising cleavage, broad implications understanding virus–host interactions inform development therapeutic strategies against other enteroviruses.

Язык: Английский

Процитировано

0