朗格特病毒通过降低gp130蛋白水平来抑制gp130/JAK/STAT信号传递
Shaoli Lin1, Xiaochun Wang1, Bhargava Teja Sallapalli1
1Molecular Virology Laboratory, Virginia-Maryland College of Veterinary Medicine, University of Maryland, College Park, MD, USA.
Journal of medical virology
|March 27, 2024
概括
朗格特病毒 (LGTV) 和传染性脑炎病毒 (TBEV) 抑制gp130/JAK/STAT信号通路. 这种病毒干扰会影响宿主细胞的反应,并为新型抗病毒疗法和疫苗提供点.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 感染性脑炎病毒 (TBEV) 血清复合体导致严重的神经侵入性疾病.
- 朗格特病毒 (LGTV),TBEV的亲属,以较低的致病性模拟病毒与宿主相互作用.
- gp130/JAK/STAT信号对生物过程和免疫反应至关重要.
研究的目的:
- 研究LGTV感染对gp130/JAK/STAT信号传输的影响.
- 阐明病毒蛋白在调节这种途径中的作用.
- 探索基于这些相互作用的潜在抗病毒策略.
主要方法:
- 评估在LGTV感染细胞中通过哥斯塔丁M (OSM) 刺激的STAT3酸化和核转位.
- 在感染细胞中测量JAK1激活和gp130蛋白表达.
- 评估LGTV NS5蛋白和TBEV感染对gp130水平的影响.
- 研究OSM预处理的抗病毒作用和STAT1/STAT2.2的作用.
主要成果:
- 在OSM刺激时,LGTV感染显著降低了化STAT3 (pSTAT3) 水平,并阻止了STAT3的核转位.
- 通过病毒NS5蛋白质的介导,LGTV抑制了JAK1的激活和减少了gp130的表达.
- 此外,TBEV感染也导致gp130水平降低.
- 在OSM前期治疗中抑制了LGTV复制,这表明STAT3介导的抗病毒机制独立于STAT1/STAT2.2.
结论:
- 由于LGTV和TBEV干扰了gp130/JAK/STAT信号通路.
- 病毒的NS5蛋白在降低gp130表达的调节中起作用.
- 由OSM诱导的抗病毒作用似乎由STAT3信号介导.
- 了解这些病毒与宿主相互作用为开发新的抗病毒疗法和针对TBEV和相关黄病毒的疫苗提供了基础.
相关概念视频
The JAK-STAT Signaling Pathway
8.9K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.9K
Amplifying Signals via Enzymatic Cascade
8.5K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.5K
PI3K/mTOR/AKT Signaling Pathway
3.5K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.5K
cAMP-dependent Protein Kinase Pathways
6.3K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.3K
GPCR Desensitization
6.0K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
6.0K
TGF - β Signaling Pathway
7.3K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.3K


