Ku80 autoantigen as a cellular coreceptor for human parvovirus B19 infection
Ku80 autoantigen as a cellular coreceptor for human parvovirus B19 infection
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DOI：
10.1182/blood-2005-02-0536
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发表时间：
2005-11-15
期刊：
影响因子：
20.3
通讯作者：
Sasaki, T
中科院分区：
文献类型：
--
作者：
Munakata, Y;Saito-Ito, T;Sasaki, T
人细小病毒B19（B19）感染表达P抗原的人红系细胞。然而，一些P抗原阳性的细胞系未能结合B19，而一些细胞系尽管P抗原的表达不可检测，但仍具有结合B19的能力。我们在这里证明，B19特异性结合细胞表面上的Ku80自身抗原。此外，用Ku80基因转染HeLa细胞使B19能够结合并允许其进入细胞。此外，Ku80的短干扰RNA在KU812Ep6细胞中的细胞表面表达的Ku80的减少，这是一个对B19感染高度敏感的细胞系，导致B19结合在KU812Ep6细胞中的显著抑制。尽管Ku80最初被描述为核蛋白，但具有血型糖蛋白A或CD 36的人骨髓红细胞系细胞、具有CD 20的B细胞或具有CD 3的T细胞均对Ku80的细胞表面表达呈阳性。在抗Ku80抗体的存在下，B19对KU812Ep6细胞和骨髓细胞的感染被抑制。我们的数据表明，Ku80功能作为一种新的辅助受体的B19感染，这一发现可能提供了一个解释的病理免疫与B19感染。
Human parvovirus B19 (B19) infects human erythroid cells expressing P antigen. However, some cell lines that were positive for P antigen failed to bind B19, whereas some cell lines had an ability to bind B19 despite undetectable expression of P antigen. We here demonstrate that B19 specifically binds with Ku80 autoantigen on the cell surface. Furthermore, transfection of HeLa cells with the gene of Ku80 enabled the binding of B19 and allowed its entry into cells. Moreover, reduction of cell-surface expression of Ku80 in KU812Ep6 cells, which was a high-sensitive cell line for B19 infection, by short interfering RNA for Ku80 resulted in the marked inhibition of B19 binding in KU812Ep6 cells. Although Ku80 originally has been described as a nuclear protein, human bone marrow erythrold cells with glycophorin A or CD36, B cells with CD20, or T cells with CD3 were all positive for cell-surface expression of Ku80. B19 infection of KU812Ep6 cells and bone marrow cells was inhibited in the presence of anti-Ku80 antibody. Our data suggest that Ku80 functions as a novel coreceptor for B19 infection, and this finding may provide an explanation for the pathologic immunity associated with B19 infection.