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灵长类细小病毒 VP1u 中的保守受体结合结构域决定了对红细胞的明显嗜性。

A Conserved Receptor-Binding Domain in the VP1u of Primate Erythroparvoviruses Determines the Marked Tropism for Erythroid Cells.

机构信息

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

CSL Behring AG, 3000 Bern, Switzerland.

出版信息

Viruses. 2022 Feb 17;14(2):420. doi: 10.3390/v14020420.

DOI:10.3390/v14020420
PMID:35216013
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8879732/
Abstract

Parvovirus B19 (B19V) is a human pathogen with a marked tropism for erythroid progenitor cells (EPCs). The N-terminal of the VP1 unique region (VP1u) contains a receptor-binding domain (RBD), which mediates virus uptake through interaction with an as-yet-unknown receptor (VP1uR). Considering the central role of VP1uR in the virus tropism, we sought to investigate its expression profile in multiple cell types. To this end, we established a PP7 bacteriophage-VP1u bioconjugate, sharing the size and VP1u composition of native B19V capsids. The suitability of the PP7-VP1u construct as a specific and sensitive VP1uR expression marker was validated in competition assays with B19V and recombinant VP1u. VP1uR expression was exclusively detected in erythroid cells and cells reprogrammed towards the erythroid lineage. Sequence alignment and in silico protein structure prediction of the N-terminal of VP1u (N-VP1u) from B19V and other primate erythroparvoviruses (simian, rhesus, and pig-tailed) revealed a similar structure characterized by a fold of three or four α-helices. Functional studies with simian parvovirus confirmed the presence of a conserved RBD in the N-VP1u, mediating virus internalization into human erythroid cells. In summary, this study confirms the exclusive association of VP1uR expression with cells of the erythroid lineage. The presence of an analogous RBD in the VP1u from non-human primate erythroparvoviruses emphasizes their parallel evolutionary trait and zoonotic potential.

摘要

细小病毒 B19（B19V）是一种具有明显红系祖细胞（EPC）趋向性的人类病原体。VP1 独特区（VP1u）的 N 端含有一个受体结合域（RBD），通过与未知受体（VP1uR）相互作用介导病毒摄取。鉴于 VP1uR 在病毒趋向性中的核心作用，我们试图研究其在多种细胞类型中的表达谱。为此，我们建立了一种 PP7 噬菌体-VP1u 生物缀合物，其大小和 VP1u 组成与天然 B19V 衣壳相同。在与 B19V 和重组 VP1u 的竞争实验中，验证了 PP7-VP1u 构建体作为特异性和敏感 VP1uR 表达标志物的适用性。VP1uR 表达仅在红系细胞和向红系谱系重编程的细胞中检测到。对 B19V 和其他灵长类动物红系细小病毒（猴、恒河猴和猪尾）的 VP1u 的 N 端（N-VP1u）的序列比对和计算机蛋白质结构预测显示，具有相似结构的特征是三个或四个α-螺旋的折叠。用猴细小病毒进行的功能研究证实了 N-VP1u 中存在保守的 RBD，介导病毒内吞进入人红系细胞。总之，这项研究证实了 VP1uR 表达与红系细胞的专属性关联。非灵长类动物红系细小病毒 VP1u 中存在类似的 RBD，强调了它们平行进化的特征和人畜共患的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e141/8879732/0fcae878a286/viruses-14-00420-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e141/8879732/353711aae198/viruses-14-00420-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e141/8879732/5d81205f79b2/viruses-14-00420-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e141/8879732/837819182706/viruses-14-00420-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e141/8879732/2f93052d7575/viruses-14-00420-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e141/8879732/dea2f8768287/viruses-14-00420-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e141/8879732/0fcae878a286/viruses-14-00420-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e141/8879732/353711aae198/viruses-14-00420-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e141/8879732/5d81205f79b2/viruses-14-00420-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e141/8879732/837819182706/viruses-14-00420-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e141/8879732/2f93052d7575/viruses-14-00420-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e141/8879732/dea2f8768287/viruses-14-00420-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e141/8879732/0fcae878a286/viruses-14-00420-g006.jpg

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