Zou Wei, Ning Kang, Xu Peng, Deng Xuefeng, Cheng Fang, Kleiboeker Steve, Qiu Jianming
Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USA.
Department of Research and Development, Viracor Eurofins Laboratories, Lee's Summit, Missouri, USA.
J Virol. 2021 Jun 24;95(14). doi: 10.1128/JVI.00466-21. Epub 2021 May 5.
Parvovirus B19 (B19V) infection causes diseases in humans ranging from the mild to severe hematological disorders. The unique region of the minor structural protein VP1 (VP1u) of 227 amino acids harbors strong neutralizing epitopes which elicit dominant immune responses in patients. Recent studies have shown that the VP1u selectively binds to and enters B19V permissive cells through an unknown cellular proteinaceous receptor. In the present study, we demonstrated that purified recombinant VP1u effectively inhibits B19V infection of expanded primary human erythroid progenitors. Furthermore, we identified the amino acid sequence 5-68 of the VP1 (VP1u) is sufficient to confer the inhibition of B19V infection at a level similar to that of the full-length VP1u. structure prediction suggests that the VP1u contains three α-helices. Importantly, we found that the inhibition capability of the minimal domain VP1u is independent of its dimerization but is likely dependent on the structure of the three predicated α-helices. As VP1u outcompetes the full-length VP1u in entering cells, we believe that VP1u functions as a receptor-binding ligand during virus entry. Finally, we determined the effective inhibition potency of VP1u in B19V infection of human erythroid progenitors, which has a half maximal effective concentration (EC) of 67 nM, suggesting an anti-viral peptide candidate to combat B19V infection.Human parvovirus B19 infection causes severe hematological disorders, including transient aplastic crisis, pure red cell aplasia, and hydrops fetalis. A productive B19 infection is highly restricted to human erythroid progenitors in human bone marrow and fetal liver. In the current study, we identified that the N-terminal 5-68 amino acids domain of the minor viral capsid protein VP1 enters expanded human erythroid progenitors, which is nearly 5 times more efficient than the full-length VP1 unique region (1-227aa). Importantly, purified recombinant 5-68aa of the VP1 has a high efficiency in inhibition of parvovirus B19 infection of human erythroid progenitors, which has a half maximal effective concentration (EC) of 67 nM and a low cytotoxicity. The N-terminal 5-68 amino acids holds the potential as an effective antiviral of parvovirus B19 caused hematological disorders, as well as a carrier to deliver proteins to human erythroid progenitors.
细小病毒B19（B19V）感染可导致人类从轻度到严重血液系统疾病的各种病症。微小结构蛋白VP1的227个氨基酸的独特区域（VP1u）含有强大的中和表位，可在患者体内引发主要的免疫反应。最近的研究表明，VP1u通过一种未知的细胞蛋白质受体选择性地结合并进入B19V允许性细胞。在本研究中，我们证明纯化的重组VP1u能有效抑制原代人红细胞祖细胞的B19V感染。此外，我们确定VP1（VP1u）的5-68位氨基酸序列足以在与全长VP1u相似的水平上抑制B19V感染。结构预测表明，VP1u包含三个α螺旋。重要的是，我们发现最小结构域VP1u的抑制能力与其二聚化无关，但可能依赖于三个预测的α螺旋的结构。由于VP1u在进入细胞时比全长VP1u更具竞争力，我们认为VP1u在病毒进入过程中起受体结合配体的作用。最后，我们确定了VP1u对人红细胞祖细胞B19V感染的有效抑制效力，其半数最大有效浓度（EC）为67 nM，提示其为对抗B19V感染的抗病毒肽候选物。人细小病毒B19感染可导致严重血液系统疾病，包括暂时性再生障碍危象、纯红细胞再生障碍和胎儿水肿。B19的有效感染高度局限于人类骨髓和胎儿肝脏中的人红细胞祖细胞。在当前研究中，我们确定病毒小衣壳蛋白VP1的N端5-68个氨基酸结构域可进入原代人红细胞祖细胞，其效率比全长VP1独特区域（1-227aa）高近5倍。重要的是，纯化的重组VP1的5-68aa对人红细胞祖细胞的细小病毒B19感染具有高效抑制作用，其半数最大有效浓度（EC）为67 nM，且细胞毒性低。N端5-68个氨基酸有潜力成为治疗细小病毒B19引起的血液系统疾病的有效抗病毒药物，以及将蛋白质递送至人红细胞祖细胞的载体。
