Dataset Information

Glycoprotein Non-Metastatic Melanoma Protein B Restricts PRRSV Replication by Inhibiting Autophagosome-Lysosome Fusion.

ABSTRACT: Glycoprotein non-metastatic melanoma protein B (GPNMB) is a transmembrane protein enriched on the surface of some cells, including melanoma, glioblastoma, and macrophages. GPNMB has been reported to have multifaceted roles, such as facilitating cell-cell adhesion and migration, stimulating kinase signaling, and regulating inflammation. Porcine reproductive and respiratory syndrome virus (PRRSV) is the leading cause of severe economic loss in the swine industry worldwide. In this study, the role of GPNMB was investigated in porcine alveolar macrophages during PRRSV infection. We observed that GPNMB expression was markedly reduced in PRRSV-infected cells. The inhibition of GPNMB by specific small interfering RNA led to an enhancement in virus yields, and GPNMB overexpression decreased PRRSV replication. Further studies revealed that the overexpression of GPNMB could induce the accumulation of autophagosome through inhibiting autophagosome-lysosome fusion. Using a specific inhibitor, we confirmed that the inhibition of autophagosome-lysosome fusion significantly inhibited viral replication. Taken together, our data demonstrate that GPNMB inhibits PRRSV replication by inhibiting the autophagosome-lysosome fusion and provides a novel therapeutic target for virus infection.

SUBMITTER: Xu Y

PROVIDER: S-EPMC10143855 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Glycoprotein Non-Metastatic Melanoma Protein B Restricts PRRSV Replication by Inhibiting Autophagosome-Lysosome Fusion.

Xu Yunfei Y Wang Mengjie M Zhang Lin L Pan Yu Y Zhang Wenli W Ma Wenjie W Chen Hongyan H Tang Lijie L Xia Changyou C Wang Yue Y

Viruses 20230405 4

Glycoprotein non-metastatic melanoma protein B (GPNMB) is a transmembrane protein enriched on the surface of some cells, including melanoma, glioblastoma, and macrophages. GPNMB has been reported to have multifaceted roles, such as facilitating cell-cell adhesion and migration, stimulating kinase signaling, and regulating inflammation. Porcine reproductive and respiratory syndrome virus (PRRSV) is the leading cause of severe economic loss in the swine industry worldwide. In this study, the role ...[more]

PMID: 37112900

Similar Datasets

Project description:Macroautophagy/autophagy is a conserved ubiquitous pathway that performs diverse roles in health and disease. Although many key, widely expressed proteins that regulate autophagosome formation followed by lysosomal fusion have been identified, the possibilities of cell-specific elements that contribute to the autophagy fusion machinery have not been explored. Here we show that a macrophage-specific isoform of the vacuolar ATPase protein ATP6V0D2/subunit d2 is dispensable for lysosome acidification, but promotes the completion of autophagy via promotion of autophagosome-lysosome fusion through its interaction with STX17 and VAMP8. Atp6v0d2-deficient macrophages have augmented mitochondrial damage, enhanced inflammasome activation and reduced clearance of Salmonella typhimurium. The susceptibility of atp6v0d2 knockout mice to DSS-induced colitis and Salmonella typhimurium-induced death, highlights the in vivo significance of ATP6V0D2-mediated autophagosome-lysosome fusion. Together, our data identify ATP6V0D2 as a key component of macrophage-specific autophagosome-lysosome fusion machinery maintaining macrophage organelle homeostasis and, in turn, limiting both inflammation and bacterial infection. Abbreviations: ACTB/β-actin: actin, beta; ATG14: autophagy related 14; ATG16L1: autophagy related 16-like 1 (S. cerevisiae); ATP6V0D1/2: ATPase, H+ transporting, lysosomal V0 subunit D1/2; AIM2: absent in melanoma 2; BMDM: bone marrow-derived macrophage; CASP1: caspase 1; CGD: chronic granulomatous disease; CSF1/M-CSF: colony stimulating factor 1 (macrophage); CTSB: cathepsin B; DSS: dextran sodium sulfate; IL1B: interleukin 1 beta; IL6: interleukin 6; IRGM: immunity-related GTPase family M member; KO: knockout; LAMP1: lysosomal-associated membrane protein 1; LC3: microtubule-associated protein 1 light chain 3; LPS: lipo-polysaccaride; NLRP3: NLR family, pyrin domain containing 3; PYCARD/ASC: PYD and CARD domain containing; SNARE: soluble N-ethylmaleimide-sensitive factor attachment protein receptor; SNAP29: synaptosomal-associated protein 29; SQSTM1/p62: sequestosome 1; STX17: syntaxin 17; TLR: toll-like receptor; TNF: tumor necrosis factor ; TOMM20: translocase of outer mitochondrial membrane 20; ULK1: unc-51 like kinase 1; VAMP8: vesicle-associated membrane protein 8; WT: wild type; 3-MA: 3-methyladenine.

Dataset Information

Glycoprotein Non-Metastatic Melanoma Protein B Restricts PRRSV Replication by Inhibiting Autophagosome-Lysosome Fusion.

Publications

Glycoprotein Non-Metastatic Melanoma Protein B Restricts PRRSV Replication by Inhibiting Autophagosome-Lysosome Fusion.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets