MARCH8 Targets Cytoplasmic Lysine Residues of Various Viral Envelope Glycoproteins.
MARCH8 Targets Cytoplasmic Lysine Residues of Various Viral Envelope Glycoproteins.
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DOI：
10.1128/spectrum.00618-21
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发表时间：
2022-02-23
影响因子：
3.7
通讯作者：
Tokunaga K
中科院分区：
文献类型：
--
作者：
Zhang Y;Ozono S;Tada T;Tobiume M;Kameoka M;Kishigami S;Fujita H;Tokunaga K
宿主跨膜蛋白MARCH 8是环指E3泛素连接酶，其下调多种宿主跨膜蛋白，如MHC-II。我们最近报道，MARCH 8在病毒产生细胞中的表达通过两种不同的途径降低病毒粒子不仅与HIV-1包膜糖蛋白而且与水疱性口炎病毒G-糖蛋白的结合来削弱病毒的感染性。然而，MARCH 8抑制谱在很大程度上仍然未知。在这里，我们显示了MARCH 8的抗病毒谱，使用各种病毒包膜糖蛋白进行假型化。感染实验显示，来自弹状病毒、沙粒病毒、冠状病毒和披膜病毒（甲病毒）家族的病毒包膜糖蛋白对MARCH 8介导的抑制敏感。狂犬病病毒-G、淋巴细胞性脉络丛脑膜炎病毒糖蛋白、SARS-CoV和SARS-CoV-2刺突蛋白、基孔肯雅病毒和罗斯河病毒E2蛋白质的胞质尾部的赖氨酸突变赋予了对MARCH 8的抗性。免疫荧光显示，受损的下调这些病毒包膜糖蛋白的突变体的MARCH 8，随后由溶酶体降解，这表明MARCH 8介导的泛素化导致这些信封的细胞内降解。事实上，狂犬病病毒-G和基孔肯雅病毒E2蛋白被证明是明显的泛素化。我们得出结论，MARCH 8对多种病毒包膜糖蛋白具有抑制活性，这些病毒包膜糖蛋白的细胞质赖氨酸残基是这种抗病毒因子的靶向。重要性MARCH E3泛素连接酶家族的成员MARCH 8下调许多不同种类的宿主跨膜蛋白，导致细胞内稳态的调节。另一方面，MARCH 8在结合并下调HIV-1包膜糖蛋白和水疱性口炎病毒G-糖蛋白（病毒跨膜蛋白）时，可作为抗病毒因子发挥作用。这项研究表明，在细胞膜蛋白的情况下，MARCH 8显示广谱抑制各种病毒包膜糖蛋白，通过识别其细胞质赖氨酸残基，导致溶酶体降解。
The host transmembrane protein MARCH8 is a RING finger E3 ubiquitin ligase that downregulates various host transmembrane proteins, such as MHC-II. We have recently reported that MARCH8 expression in virus-producing cells impairs viral infectivity by reducing virion incorporation of not only HIV-1 envelope glycoprotein but also vesicular stomatitis virus G-glycoprotein through two different pathways. However, the MARCH8 inhibition spectrum remains largely unknown. Here, we show the antiviral spectrum of MARCH8 using viruses pseudotyped with a variety of viral envelope glycoproteins. Infection experiments revealed that viral envelope glycoproteins derived from the rhabdovirus, arenavirus, coronavirus, and togavirus (alphavirus) families were sensitive to MARCH8-mediated inhibition. Lysine mutations at the cytoplasmic tails of rabies virus-G, lymphocytic choriomeningitis virus glycoproteins, SARS-CoV and SARS-CoV-2 spike proteins, and Chikungunya virus and Ross River virus E2 proteins conferred resistance to MARCH8. Immunofluorescence showed impaired downregulation of the mutants of these viral envelope glycoproteins by MARCH8, followed by lysosomal degradation, suggesting that MARCH8-mediated ubiquitination leads to intracellular degradation of these envelopes. Indeed, rabies virus-G and Chikungunya virus E2 proteins proved to be clearly ubiquitinated. We conclude that MARCH8 has inhibitory activity on a variety of viral envelope glycoproteins whose cytoplasmic lysine residues are targeted by this antiviral factor. IMPORTANCE A member of the MARCH E3 ubiquitin ligase family, MARCH8, downregulates many different kinds of host transmembrane proteins, resulting in the regulation of cellular homeostasis. On the other hands, MARCH8 acts as an antiviral factor when it binds to and downregulates HIV-1 envelope glycoprotein and vesicular stomatitis virus G-glycoprotein that are viral transmembrane proteins. This study reveals that, as in the case of cellular membrane proteins, MARCH8 shows broad-spectrum inhibition against various viral envelope glycoproteins by recognizing their cytoplasmic lysine residues, resulting in lysosomal degradation.
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影响因子：
3.3
作者：
Eyster CA;Cole NB;Petersen S;Viswanathan K;Früh K;Donaldson JG
通讯作者：
Donaldson JG
DOI：
10.1084/jem.20092203
发表时间：
2011-01-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Tze LE;Horikawa K;Domaschenz H;Howard DR;Roots CM;Rigby RJ;Way DA;Ohmura-Hoshino M;Ishido S;Andoniou CE;Degli-Esposti MA;Goodnow CC
通讯作者：
Goodnow CC
影响因子：
3.3
作者：
Singh, Shivam;Bano, Arjumand;Sharma, Rinu
通讯作者：
Sharma, Rinu
DOI：
10.4049/jimmunol.1101643
发表时间：
2011-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Baravalle G;Park H;McSweeney M;Ohmura-Hoshino M;Matsuki Y;Ishido S;Shin JS
通讯作者：
Shin JS
影响因子：
5.4
作者：
Bartee, E;Mansouri, M;Früh, K
通讯作者：
Früh, K