Alpha5beta1 integrin as a cellular coreceptor for human parvovirus B19: requirement of functional activation of beta1 integrin for viral entry.
Alpha5beta1 integrin as a cellular coreceptor for human parvovirus B19: requirement of functional activation of beta1 integrin for viral entry.
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DOI：
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发表时间：
2003
期刊：
影响因子：
20.3
通讯作者：
Kirsten A. Weigel-Kelley;M. Yoder;A. Srivastava
中科院分区：
文献类型：
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作者：
Kirsten A. Weigel-Kelley;M. Yoder;A. Srivastava
致病性人类细小病毒B19的复制仅限于红系祖细胞。虽然P血型抗原被认为是细小病毒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的感染是不允许的。我们已经证明P抗原是与细小病毒B19结合所必需的，但不足以使病毒进入细胞。为了测试细小病毒B19是否利用细胞表面的共受体进入，我们使用了人红白血病细胞(K562)，它允许细小病毒B19结合，但不允许进入。我们在此报道，在佛波酯处理后，K562细胞对细小病毒B19的进入变得黏附和允许，这是由α5β1整合素介导的，但仅在其高亲和力构象中。成熟的人红细胞(RBC)表达高水平的P抗原，但不表达α5β1整合素，与微小病毒B19结合，但不允许病毒进入。相反，原代人类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的高效系统性传播。
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.