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 downregulation modulates profibrotic responses including myofibroblast differentiation DOI
Xia Guo, Oluwaseun Adeyanju, Ayobami Matthew Olajuyin

et al.

AJP Cell Physiology, Journal Year: 2023, Volume and Issue: 325(5), P. C1190 - C1200

Published: Sept. 4, 2023

Interstitial lung diseases can result in poor patient outcomes, especially idiopathic pulmonary fibrosis (IPF), a severe interstitial disease with unknown causes. The lack of treatment options requires further understanding the pathological process/mediators. Membrane-associated RING-CH 8 (MARCH8) has been implicated immune function regulation and inflammation, however, its role development particularly fibroblast to myofibroblast transition (FMT) remains gap existing knowledge. In this study, we demonstrated decreased MARCH8 expression patients IPF compared non-PF controls bleomycin-induced PF. TGF-β dose- time-dependently normal human (HLFs), along induction FMT markers α-SMA, collagen type I (Col-1), fibronectin (FN). Interestingly, overexpression significantly suppressed TGF-β-induced Col-1, FN. By contrast, knockdown using siRNA upregulated basal α-SMA/Col-1/FN. Moreover, enhanced marker expression. These data clearly show that is critical "brake" for potentially affects We found mRNA proteasome inhibitor MG132 failed block decrease induced by TGF-β. Conversely, decreases levels time-dependent manner, suggesting transcriptional Mechanistically, Smad2/3 phosphorylation, which may account observed effects. Taken together, study an unrecognized negatively regulating profibrogenic responses relevant diseases.

Language: Английский

Citations

1

Further Characterization of the Antiviral Transmembrane Protein MARCH8 DOI Creative Commons
Takuya Tada, Yanzhao Zhang, D. J. Kong

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(8), P. 698 - 698

Published: April 17, 2024

The cellular transmembrane protein MARCH8 impedes the incorporation of various viral envelope glycoproteins, such as HIV-1 glycoprotein (Env) and vesicular stomatitis virus G-glycoprotein (VSV-G), into virions by downregulating them from surface virus-producing cells. This downregulation significantly reduces efficiency infection. In this study, we aimed to further characterize host investigating its species specificity domains responsible for antiviral activity, well ability inhibit cell-to-cell We found that function is conserved in rhesus macaque, mouse, bovine versions. RING-CH these versions are functionally important inhibiting Env VSV-G-pseudovirus infection, whereas tyrosine motifs crucial former only, consistent with findings human MARCH8. Through analysis chimeric proteins between non-antiviral MARCH3, determined both N-terminal C-terminal cytoplasmic tails, presumably domain, critical activity. Notably, unable block likely due insufficient Env. These offer insights understanding biology protein.

Language: Английский

Citations

0

Ubiquitination in viral entry and replication: Mechanisms and implications DOI

Maria Velez-Brochero,

Padmanava Behera,

Kazi Sabrina Afreen

et al.

Advances in virus research, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 38

Published: Jan. 1, 2024

Language: Английский

Citations

0

AP3B1 facilitates PDIA3/ERP57 function to regulate rabies virus glycoprotein selective degradation and viral entry DOI

Yuelan Zhang,

Xinyi Zhang, Xueli Yang

et al.

Autophagy, Journal Year: 2024, Volume and Issue: 20(12), P. 2785 - 2803

Published: Aug. 12, 2024

Rabies virus causes an estimated 59,000 annual fatalities worldwide and promising therapeutic treatments are necessary to develop. In this study, affinity tag-purification mass spectrometry was employed delineate RABV glycoprotein host protein interactions, PDIA3/ERP57 identified as a potential inhibitor of infection. PDIA3 restricted infection with follow mechanisms: mediated the degradation G by targeting lysine 332 via selective macroautophagy/autophagy pathway; The interactor, AP3B1 (adaptor related complex 3 subunit beta 1) indispensable in PDIA3-triggered protein; Furthermore, competitively bound NCAM1/NCAM (neural cell adhesion molecule block G, hindering viral entry into cells. 190-199 aa residues were sufficient defend against RABV. These results demonstrated biologics that target or utilize peptide treat clinical rabies.

Language: Английский

Citations

0

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

Citations

0