Human fibroblast growth factor receptor 1 is a co-receptor for infection by adeno-associated virus 2
Human fibroblast growth factor receptor 1 is a co-receptor for infection by adeno-associated virus 2
复制标题
DOI：
10.1038/4758
复制
发表时间：
1999-01-01
期刊：
影响因子：
82.9
通讯作者：
Srivastava, A
中科院分区：
文献类型：
--
作者：
Qing, K;Mah, C;Srivastava, A
基于腺相关病毒2（AAV）的载体作为用于人类基因治疗的更常用的逆转录病毒和腺病毒载体的潜在有用的替代物而受到关注。虽然AAV使用广泛表达的细胞表面硫酸乙酰肝素蛋白聚糖（HSPG）作为受体，但AAV载体的转导效率在体外和体内的不同细胞和组织中变化很大。我们在这里证明，HSPG单独的细胞表面表达是不够的AAV感染，并且AAV还需要人成纤维细胞生长因子受体1（FGFR1）作为成功的病毒进入宿主细胞的共受体。我们记录了不表达HSPG或FGFR 1的细胞不能结合AAV，因此对AAV感染具有抗性。在用编码鼠HSPG和人FGFR 1的cDNA稳定转染后，这些非允许细胞被AAV载体成功转导。此外，已知表达FGFR 1和表皮生长因子受体两者的允许细胞的AAV感染通过用碱性成纤维细胞生长因子而不是用表皮生长因子处理细胞而被消除。FGFR1作为AAV共受体的鉴定不仅为它在AAV生命周期中的作用提供了新的见解，而且还为AAV载体在人类基因治疗中的最佳使用提供了新的见解。
Adeno-associated virus 2 (AAV)-based vectors have gained attention as a potentially useful alternative to the more commonly used retroviral and adenoviral vectors for human gene therapy. Although AAV uses the ubiquitously expressed cell surface heparan sulfate proteoglycan (HSPG) as a receptor, the transduction efficiency of AAV vectors varies greatly in different cells and tissues in vitro and in vivo. We demonstrate here that cell surface expression of HSPG alone is insufficient for AAV infection, and that AAV also requires human fibroblast growth factor receptor 1 (FGFR1) as a co-receptor for successful viral entry into the host cell. We document that cells that do not express either HSPG or FGFR1 fail to bind AAV and, consequently, are resistant to infection by AAV. These non-permissive cells are successfully transduced by AAV vectors after stable transfections with cDNAs encoding the murine HSPG and the human FGFR1. Furthermore, AAV infection of permissive cells, known to express both FGFR1 and the epidermal growth factor receptor, is abrogated by treatment of cells with basic fibroblast growth factor, but not with epidermal growth factor. The identification of FGFR1 as a co-receptor for AAV should provide new insights not only into its role in the life cycle of AAV, but also in the optimal use of AAV vectors in human gene therapy.