FBXW8 suppresses PDCoV proliferation via the NPD52-dependent autophagic degradation of a viral nucleocapsid protein DOI Creative Commons
Likai Ji,

Liying Zhou,

Ying Wang

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 18, 2024

Porcine deltacoronavirus (PDCoV), a newly discovered intestinal coronavirus, has rapidly spread among pigs worldwide and shown the potential for cross-species infection. However, interaction mechanism between PDCoV host’s antiviral response is still poorly understood. In this study, an E3 ubiquitin ligase FBXW8 was explored on proliferation. Our findings demonstrate that infection increases expression of through p65-mediated activation its promoter. We also suppresses replication by directly targeting inducing degradation PDCoV-encoded nucleocapsid (N) protein. Interestingly, catalyzes K48-linked polyubiquitination N protein at unique lysine-rich region (KR). Furthermore, we observed FBXW8-ubiquitinated interacts with NDP52, cargo receptor, leading to autophagic instead proteasomal degradation. summary, these reveal as novel host factor involved in It mediates NDP52-dependent These results provide new insights target defenses against PDCoV.

Language: Английский

MARCH8 promotes the proteasomal degradation of foot-and-mouth disease virus VP1, VP2, and VP3 to negatively regulate viral replication DOI Creative Commons

Mengge Yin,

Xiangmin Li, Min Zhang

et al.

Veterinary Research, Journal Year: 2025, Volume and Issue: 56(1)

Published: April 30, 2025

The host cell membrane-associated RING-CH8 protein (MARCH8) functions as an antiviral factor by targeting viral envelope glycoproteins. Foot-and-mouth disease virus (FMDV) is a non-enveloped, positive-sense, single-stranded RNA virus. potential impact of MARCH8 on FMDV replication remains uncertain. Here, we found that the overexpression significantly inhibited in dose-dependent manner. Conversely, knockdown facilitated replication. Specifically, interacted with VP1, VP2, and VP3, mediating their degradation proteasome-dependent catalyzed K33-linked polyubiquitination VP3. Moreover, Lys210 residue Lys63 Lys118 VP3 were identified critical target sites for MARCH8-mediated degradation. Overall, conclude intrinsic against FMDV.

Language: Английский

Citations

0
Elucidating cellular interactome of chikungunya virus identifies host dependency factors DOI Creative Commons
Peiqi Yin,

Xia Jian,

Yihan Liu

et al.

Virologica Sinica, Journal Year: 2023, Volume and Issue: 38(4), P. 497 - 507

Published: May 12, 2023

Chikungunya virus (CHIKV) is a re-emerging mosquito-transmitted RNA causing joint and muscle pain. To better understand how CHIKV rewires the host cell usurps functions, we generated systematic CHIKV-human protein-protein interaction map revealed several novel connections that will inform further mechanistic studies. One of these interactions, between viral protein E1 STIP1 homology U-box containing 1 (STUB1), was found to mediate ubiquitination degrade through proteasome. Capsid associated with G3BP1, G3BP2 AAA+ ​ATPase valosin-containing (VCP). Furthermore, VCP inhibitors blocked infection, suggesting could serve as therapeutic target. Further work required fully functional consequences interactions. Given proteins are conserved across alphaviruses, many virus-host interactions identified in this study might also exist other alphaviruses. Construction interactome provides basis for studying function alphavirus biology.

Language: Английский

Citations

9
Role of E3 ubiquitin ligases and deubiquitinating enzymes in SARS-CoV-2 infection DOI Creative Commons

Mingjiu Zhao,

Mengdi Zhang, Yang Zhou

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: June 9, 2023

Ever since its emergence in 2019, COVID-19 has rapidly disseminated worldwide, engendering a pervasive pandemic that profoundly impacted healthcare systems and the socio-economic milieu. A plethora of studies been conducted targeting pathogenic virus, SARS-CoV-2, to find ways combat COVID-19. The ubiquitin-proteasome system (UPS) is widely recognized as crucial mechanism regulates human biological activities by maintaining protein homeostasis. Within UPS, ubiquitination deubiquitination, two reversible modifications, substrate proteins have extensively studied implicated pathogenesis SARS-CoV-2. regulation E3 ubiquitin ligases DUBs(Deubiquitinating enzymes), which are key enzymes involved modification processes, determines fate proteins. Proteins associated with SARS-CoV-2 may be retained, degraded, or even activated, thus affecting ultimate outcome confrontation between host. In other words, clash host can viewed battle for dominance over DUBs, from standpoint regulation. This review primarily aims clarify mechanisms virus utilizes along own viral similar enzyme activities, facilitate invasion, replication, escape, inflammation. We believe gaining better understanding role DUBs offer novel valuable insights developing antiviral therapies.

Language: Английский

Citations

7
Functional and structural segregation of overlapping helices in HIV-1 DOI Creative Commons
Maliheh Safari, Bhargavi Jayaraman,

Henni Zommer

et al.

eLife, Journal Year: 2022, Volume and Issue: 11

Published: May 5, 2022

Overlapping coding regions balance selective forces between multiple genes. One possible division of nucleotide sequence is that the predominant force on a particular can be attributed to just one gene. While this arrangement has been observed in which gene structured and other disordered, we sought explore how overlapping genes constraints when both protein products are over same sequence. We use combination analysis, functional assays, selection experiments examine an overlapped region HIV-1 encodes helical Env Rev. find segregation occurs even overlap, with each spacing its residues manner allows mutable non-binding face helix encode important charged helix. Additionally, our reveal novel critical have implications for therapeutic targeting HIV-1.

Language: Английский

Citations

11
Transcriptome screening identifies TIPARP as an antiviral host factor against the Getah virus DOI
Houqi Jiao,

Ziqing Yan,

Xiaofeng Zhai

et al.

Journal of Virology, Journal Year: 2023, Volume and Issue: 97(10)

Published: Sept. 28, 2023

Alphaviruses threaten public health continuously, and Getah virus (GETV) is a re-emerging alphavirus that can potentially infect humans. Approved antiviral drugs vaccines against alphaviruses are few available, but several host factors have been reported. Here, we used GETV as model of to screen for additional factors. Tetrachlorodibenzo-p-dioxin-inducible poly(ADP ribose) polymerase was identified inhibit replication by inducing ubiquitination the glycoprotein E2, causing its degradation recruiting E3 ubiquitin ligase membrane-associated RING-CH8 (MARCH8). Using virus, focusing on relationship between viral structural proteins provides new insights studies alphaviruses.

Language: Английский

Citations

6
TRIM32 inhibits Venezuelan equine encephalitis virus infection by targeting a late step in viral entry DOI Creative Commons
Yifan Xie, Jie Cao,

Shuyi Gan

et al.

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(11), P. e1012312 - e1012312

Published: Nov. 11, 2024

Alphaviruses are mosquito borne RNA viruses that a reemerging public health threat. have broad host range, and can cause diverse disease outcomes like arthritis, encephalitis. The ubiquitin proteasome system (UPS) plays critical roles in regulating cellular processes to control the infections with various viruses, including alphaviruses. Previous studies suggest alphaviruses hijack UPS for virus infection, but molecular mechanisms remain poorly characterized. In addition, whether certain E3 ligases or deubiquitinases act as alphavirus restriction factors remains understood. Here, we employed cDNA expression screen identify ligase TRIM32 novel intrinsic factor against VEEV-TC83, SINV, ONNV. Ectopic of reduces whereas depletion CRISPR-Cas9 increases infection. We demonstrate inhibits through mechanism is independent TRIM32-STING-IFN axis. Combining reverse genetics biochemical assays, found interferes genome translation after membrane fusion, prior replication incoming viral genome. Furthermore, our data indicate monoubiquitination important its antiviral activity. Notably, also show two pathogenic mutants R394H D487N, related Limb-girdle muscular dystrophy (LGMD), loss activity VEEV-TC83. Collectively, these results reveal acts suppressing infection provides insights into interaction between UPS.

Language: Английский

Citations

2
When RING finger family proteins meet SARS‐CoV‐2 DOI
Chunmei Cai, Yan‐Dong Tang, Chunfu Zheng

et al.

Journal of Medical Virology, Journal Year: 2022, Volume and Issue: 94(7), P. 2977 - 2985

Published: March 8, 2022

Abstract The pandemic coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome 2 (SARS‐CoV‐2), is currently the most formidable challenge to humankind. Understanding complicated virus‐host interplay crucial for fighting against viral infection. A growing number of studies point critical roles RING (really interesting new gene) finger (RNF) proteins during SARS‐CoV‐2 RNF exert direct antiviral activity targeting genome and envelope glycoproteins SARS‐CoV‐2. Additionally, some members serve as potent regulators innate immunity antibody‐dependent neutralization Notably, also hijacks proteins‐mediated ubiquitination process evade host enhance replication. In this mini‐review, we discuss diverse mechanisms immune evasion in an proteins‐dependent manner. crosstalk between infection would help design potential novel targets COVID‐19 treatment.

Language: Английский

Citations

8
TRIM32 inhibits Venezuelan Equine Encephalitis Virus Infection by targeting a late step in viral entry DOI Creative Commons
Yifan Xie, Jie Cao,

Shuyi Gan

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 4, 2024

Alphaviruses are mosquito borne RNA viruses that a reemerging public health threat. have broad host range, and can cause diverse disease outcomes like arthritis, encephalitis. The ubiquitin proteasome system (UPS) plays critical roles in regulating cellular processes to control the infections with various viruses, including alphaviruses. Previous studies suggest alphaviruses hijack UPS for virus infection, but molecular mechanisms remain poorly characterized. In addition, whether certain E3 ligases or deubiquitinases act as alphavirus restriction factors remains understood. Here, we employed cDNA expression screen identify ligase TRIM32 novel intrinsic factor against VEEV-TC83, SINV, ONNV. Ectopic of reduces whereas depletion CRISPR-Cas9 increases infection. We demonstrate inhibits through mechanism is independent TRIM32-STING-IFN axis. Combining reverse genetics biochemical assays, found interferes genome translation after membrane fusion, prior replication incoming viral genome. Furthermore, our data indicate monoubiquitination important its antiviral activity. Notably, also show two pathogenic mutants R394H D487N, related Limb-girdle muscular dystrophy (LGMD), loss activity VEEV-TC83. Collectively, these results reveal acts suppressing infection provides insights into interaction between UPS.

Language: Английский

Citations

1
Targeting the Ubiquitin Proteasome System to Combat Influenza A Virus: Hijacking the Cleanup Crew DOI Creative Commons
Vandana Anang,

L. Antonescu,

Richard Nho

et al.

Reviews in Medical Virology, Journal Year: 2024, Volume and Issue: 34(6)

Published: Nov. 1, 2024

Influenza A virus (IAV) remains a significant global public health threat, causing substantial illness and economic burden. Despite existing antiviral drugs, the emergence of resistant strains necessitates alternative therapeutic strategies. This review explores complex interplay between ubiquitin proteasome system (UPS) IAV pathogenesis. We discuss how manipulates UPS to promote its lifecycle, while also highlighting host cells utilise counteract viral infection. Recent research on deubiquitinases as potential regulators infection is addressed. By elucidating multifaceted role in pathogenesis, this aims identify targets for novel interventions.

Language: Английский

Citations

1
Human MARCH1, 2, and 8 Block Ebola Virus Envelope Glycoprotein Cleavage via Targeting Furin P Domain DOI Open Access
Chunfu Zheng, Changqing Yu, Wenbo Tan

et al.

Authorea (Authorea), Journal Year: 2023, Volume and Issue: unknown

Published: May 10, 2023

Membrane-Associated Ring-CH (MARCH) family proteins were recently reported to inhibit viral replication through multiple modes of action. Previous work proved that human MARCH8 blocked Ebola virus (EBOV) glycoprotein (GP) maturation. Our study here demonstrates MARCH1 and MARCH2 share a similar pattern in restricting EBOV GP-mediated replication. Human retain GP the trans-Golgi network (TGN), reduce its surface display, impair GP-pseudotyped virions infectivity. Furthermore, we uncover host proprotein convertase (PC) furin could interact with MARCH1/2 intracellularly. Importantly, P domain is confirmed be recognized by MARCH1/2/8, which critical for their blocking activities. Besides, bovine murine also proteolytic processing. Altogether, our findings confirm different species showed relatively conserved feature processing, provide reference subsequent antiviral studies may facilitate development novel strategies antagonize enveloped infection.

Language: Английский

Citations

1