Weigel-Kelley Kirsten A, Yoder Mervin C, Srivastava Arun
Department of Microbiology and Immunology, Indiana University School of Medicine, Medical Science Bldg Rm 415-A, 635 Barnhill Dr, Indianapolis, IN 46202-5120, USA.
Blood. 2003 Dec 1;102(12):3927-33. doi: 10.1182/blood-2003-05-1522. Epub 2003 Aug 7.
Replication of the pathogenic human parvovirus B19 is restricted to erythroid progenitor cells. Although blood group P antigen has been reported to be the cell surface receptor for parvovirus B19, a number of nonerythroid cells, which express P antigen, are not permissive for parvovirus B19 infection. We have documented that P antigen is necessary for parvovirus B19 binding but not sufficient for virus entry into cells. To test whether parvovirus B19 utilizes a cell surface coreceptor for entry, we used human erythroleukemia cells (K562), which allow parvovirus B19 binding but not entry. We report here that upon treatment with phorbol esters, K562 cells become adherent and permissive for parvovirus B19 entry, which is mediated by alpha 5 beta 1 integrins, but only in their high-affinity conformation. Mature human red blood cells (RBCs), which express high levels of P antigen, but not alpha 5 beta 1 integrins, bind parvovirus B19 but do not allow viral entry. In contrast, primary human erythroid progenitor cells express high levels of both P antigen and alpha 5 beta 1 integrins and allow beta1 integrin-mediated entry of parvovirus B19. Thus, in a natural course of infection, RBCs are likely exploited for a highly efficient systemic dissemination of parvovirus B19.
致病性人类细小病毒B19的复制仅限于红系祖细胞。尽管有报道称血型P抗原是细小病毒B19的细胞表面受体，但许多表达P抗原的非红系细胞对细小病毒B19感染并不敏感。我们已证明P抗原对细小病毒B19结合是必需的，但不足以使病毒进入细胞。为了测试细小病毒B19进入细胞时是否利用细胞表面共受体，我们使用了人红白血病细胞（K562），这些细胞允许细小病毒B19结合但不允许其进入。我们在此报告，用佛波酯处理后，K562细胞变得贴壁且允许细小病毒B19进入，这是由α5β1整合素介导的，但仅在其高亲和力构象下。成熟的人类红细胞（RBC）表达高水平的P抗原，但不表达α5β1整合素，它们能结合细小病毒B19但不允许病毒进入。相反，原代人红系祖细胞表达高水平的P抗原和α5β1整合素，并允许β1整合素介导的细小病毒B19进入。因此，在自然感染过程中，红细胞可能被用于细小病毒B19的高效全身传播。
