Munakata Yasuhiko, Saito-Ito Takako, Kumura-Ishii Keiko, Huang Jie, Kodera Takao, Ishii Tomonori, Hirabayashi Yasuhiko, Koyanagi Yoshio, Sasaki Takeshi
Department of Rheumatology and Hematology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan.
Blood. 2005 Nov 15;106(10):3449-56. doi: 10.1182/blood-2005-02-0536. Epub 2005 Aug 2.
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 erythroid 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.
人细小病毒B19（B19）感染表达P抗原的人红细胞系。然而，一些P抗原呈阳性的细胞系未能结合B19，而一些细胞系尽管检测不到P抗原的表达却具有结合B19的能力。我们在此证明B19在细胞表面与Ku80自身抗原特异性结合。此外，用Ku80基因转染HeLa细胞可使B19结合并允许其进入细胞。而且，通过针对Ku80的小干扰RNA降低KU812Ep6细胞（一种对B19感染高度敏感的细胞系）表面Ku80的表达，导致KU812Ep6细胞中B19结合受到显著抑制。尽管Ku80最初被描述为一种核蛋白，但带有血型糖蛋白A或CD36的人骨髓红细胞系、带有CD20的B细胞或带有CD3的T细胞表面Ku80表达均呈阳性。在存在抗Ku80抗体的情况下，KU812Ep6细胞和骨髓细胞的B19感染受到抑制。我们的数据表明Ku80作为B19感染的一种新型共受体发挥作用，这一发现可能为与B19感染相关的病理免疫提供一种解释。
