Characterization of Bovine Foamy Virus Gag Late Assembly Domain Motifs and Their Role in Recruiting ESCRT for Budding.

Characterization of Bovine Foamy Virus Gag Late Assembly Domain Motifs and Their Role in Recruiting ESCRT for Budding.
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牛泡沫病毒 Gag 晚期组装结构域基序的表征及其在招募 ESCRT 出芽中的作用

DOI:
10.3390/v14030522
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发表时间:
2022-03-03
期刊:
Viruses
影响因子:
--
通讯作者:
Tan J
Tan J
中科院分区:
其他
文献类型:
--
作者:
Wang Z;Li R;Liu C;Qiao W;Tan J

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大量的逆转录病毒,如人类免疫缺陷病毒和原型泡沫病毒,通过Gag结构蛋白上的晚期结构域(L结构域)招募运输所需的内体分选复合体(ESCRT),以促进病毒萌发。然而,目前对牛泡沫病毒(BFV)萌发的分子机制知之甚少。在本研究中,我们报道了BFV通过GAG的L结构域招募ESCRT进行萌发。特别是,Vps4(编码空泡蛋白分类4)、Alix(编码ALG-2相互作用蛋白X)和TSG101(编码肿瘤敏感性101)的敲除表明BFV使用ESCRT进行萌发。对BFV Gag(BGag)的突变分析表明,与经典的L结构域基序相比,BGag含有两个基序P56LPI和Y103GPL,具有L结构域功能。此外,这两个L结构域对于BGag的细胞质定位是必要的,这对有效的萌发是重要的。此外,我们还证明了Alix在V区的功能位点是V498,而Tsg101的功能位点是BFV出芽的UBC样区的N69。综上所述,这些结果表明BFV通过BGag中的PLPI和YGPL L结构域基序招募ESCRT进行萌发。
A large number of retroviruses, such as human immunodeficiency virus (HIV) and prototype foamy virus (PFV), recruit the endosomal sorting complex required for transport (ESCRT) through the late domain (L domain) on the Gag structural protein for virus budding. However, little is known about the molecular mechanism of bovine foamy virus (BFV) budding. In the present study, we report that BFV recruits ESCRT for budding through the L domain of Gag. Specifically, knockdown of VPS4 (encoding vacuolar protein sorting 4), ALIX (encoding ALG-2-interacting protein X), and TSG101 (encoding tumor susceptibility 101) indicated that BFV uses ESCRT for budding. Mutational analysis of BFV Gag (BGag) showed that, in contrast to the classical L domain motifs, BGag contains two motifs, P56LPI and Y103GPL, with L domain functions. In addition, the two L domains are necessary for the cytoplasmic localization of BGag, which is important for effective budding. Furthermore, we demonstrated that the functional site of Alix is V498 in the V domain and the functional site of Tsg101 is N69 in the UBC-like domain for BFV budding. Taken together, these results demonstrate that BFV recruits ESCRT for budding through the PLPI and YGPL L domain motifs in BGag.
DOI: 10.1038/nrm2937
发表时间: 2010-08
期刊: Nature reviews. Molecular cell biology
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发表时间: 2021-02-20
期刊: Viruses
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