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人细小病毒 B19 的 VP1u:一种具有生物技术应用的多功能衣壳蛋白。

The VP1u of Human Parvovirus B19: A Multifunctional Capsid Protein with Biotechnological Applications.

机构信息

Department of Chemistry and Biochemistry, University of Bern, 3012 Bern, Switzerland.

出版信息

Viruses. 2020 Dec 18;12(12):1463. doi: 10.3390/v12121463.

Abstract

The viral protein 1 unique region (VP1u) of human parvovirus B19 (B19V) is a multifunctional capsid protein with essential roles in virus tropism, uptake, and subcellular trafficking. These functions reside on hidden protein domains, which become accessible upon interaction with cell membrane receptors. A receptor-binding domain (RBD) in VP1u is responsible for the specific targeting and uptake of the virus exclusively into cells of the erythroid lineage in the bone marrow. A phospholipase A domain promotes the endosomal escape of the incoming virus. The VP1u is also the immunodominant region of the capsid as it is the target of neutralizing antibodies. For all these reasons, the VP1u has raised great interest in antiviral research and vaccinology. Besides the essential functions in B19V infection, the remarkable erythroid specificity of the VP1u makes it a unique erythroid cell surface biomarker. Moreover, the demonstrated capacity of the VP1u to deliver diverse cargo specifically to cells around the proerythroblast differentiation stage, including erythroleukemic cells, offers novel therapeutic opportunities for erythroid-specific drug delivery. In this review, we focus on the multifunctional role of the VP1u in B19V infection and explore its potential in diagnostics and erythroid-specific therapeutics.

摘要

人细小病毒 B19(B19V)的病毒蛋白 1 独特区(VP1u)是一种多功能衣壳蛋白,在病毒嗜性、摄取和细胞内运输中起着重要作用。这些功能位于隐藏的蛋白结构域中,当与细胞膜受体相互作用时,这些结构域变得可及。VP1u 中的一个受体结合域(RBD)负责病毒的特异性靶向和摄取,仅进入骨髓中红系细胞。一个磷脂酶 A 结构域促进进入的病毒进入内体的逃逸。VP1u 也是衣壳的免疫优势区,因为它是中和抗体的靶标。由于所有这些原因,VP1u 在抗病毒研究和疫苗学中引起了极大的兴趣。除了在 B19V 感染中的重要功能外,VP1u 对红细胞的显著特异性使其成为一种独特的红细胞表面生物标志物。此外,VP1u 具有将不同货物特异性递送至原红细胞分化阶段周围细胞的能力,包括红白血病细胞,为红细胞特异性药物递送提供了新的治疗机会。在这篇综述中,我们重点讨论了 VP1u 在 B19V 感染中的多功能作用,并探讨了其在诊断和红细胞特异性治疗中的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad37/7765992/2555c4c03f86/viruses-12-01463-g001.jpg

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