Coagulation factor VIIa binds to herpes simplex virus 1-encoded glycoprotein C forming a factor X-enhanced tenase complex oriented on membranes.
Coagulation factor VIIa binds to herpes simplex virus 1-encoded glycoprotein C forming a factor X-enhanced tenase complex oriented on membranes.
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DOI：
10.1111/jth.14790
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发表时间：
2020-06
期刊：
影响因子：
--
通讯作者：
Pryzdial ELG
中科院分区：
文献类型：
--
作者：
Lin BH;Sutherland MR;Rosell FI;Morrissey JH;Pryzdial ELG
细胞膜源性凝血启动剂、组织因子（TF）和阴离子磷脂（aPL）在1型单纯疱疹病毒（HSV1）表面组成，绕过生理调节。TF和aPL通过FVIIa加速因子(F) X到FXa的蛋白水解激活，诱导凝块形成和细胞信号传导。因此，病毒表面TF增强了体内感染。hsv1编码的糖蛋白C （gC）通过提供病毒FX结合位点和增加溶液中的FVIIa功能参与了这种张力酶的活性。探讨gC对fviia依赖性FX激活的生化影响。采用免疫金电镜（IEM）、动力学显色法和微尺度热泳法（MST）对酶生化进行解剖。重组TF和gC通过用多组氨酸取代跨膜结构域进行溶解，可以定向合成含ni -螯合脂质（Ni-aPL）的单层囊泡。将这些构建体与纯化的HSV1 TF±/gC±变体进行比较。IEM证实gC， TF和aPL在单个HSV1颗粒上同时表达，其中gC对张力酶活性的贡献需要病毒TF的可用性。与病毒张力酶活性不同，sTF和sgC在与Ni-aPL结合时对FVIIa的辅因子作用是可加性的。发现FVIIa与sgC结合，FX增强了这种结合。sgC在脂质膜上的定向对于fviia依赖性FX激活至关重要。gC与FVIIa/FX的组装与TF的组装相似，可能涉及HSV1包膜上的其他成分，与病毒感染和病理有关。
The cell membrane-derived initiators of coagulation, tissue factor (TF) and anionic phospholipid (aPL) are constitutive on the herpes simplex virus type 1 (HSV1) surface, bypassing physiological regulation. TF and aPL accelerate proteolytic activation of factor (F) X to FXa by FVIIa to induce clot formation and cell signaling. Thus, infection in vivo is enhanced by virus surface TF. HSV1-encoded glycoprotein C (gC) is implicated in this tenase activity by providing viral FX binding sites and increasing FVIIa function in solution. To examine the biochemical influences of gC on FVIIa-dependent FX activation. Immunogold electron microscopy (IEM), kinetic chromogenic assays and microscale thermophoresis (MST) were used to dissect tenase biochemistry. Recombinant TF and gC were solubilized (s) by substituting the transmembrane domain with poly-histidine, which could be orientated on synthetic unilamellar vesicles containing Ni-chelating lipid (Ni-aPL). These constructs were compared to purified HSV1 TF±/gC± variants. IEM confirmed that gC, TF and aPL are simultaneously expressed on a single HSV1 particle where the contribution of gC to tenase activity required the availability of viral TF. Unlike viral tenase activity, the cofactor effects of sTF and sgC on FVIIa was additive when bound to Ni-aPL. FVIIa was found to bind to sgC and this was enhanced by FX. Orientation of sgC on a lipid membrane was critical for FVIIa-dependent FX activation. The assembly of gC with FVIIa/FX parallels that of TF and may involve other constituents on the HSV1 envelope with implications in virus infection and pathology.
影响因子：
3.7
作者：
Nuzzio KM;Watt ED;Boettcher JM;Gajsiewicz JM;Morrissey JH;Rienstra CM
通讯作者：
Rienstra CM