Tyro3 family-mediated cell entry of Ebola and Marburg viruses
Tyro3 family-mediated cell entry of Ebola and Marburg viruses
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DOI：
10.1128/jvi.01157-06
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发表时间：
2006-10-01
影响因子：
5.4
通讯作者：
Kawaoka, Yoshihiro
中科院分区：
文献类型：
--
作者：
Shimojima, Masayuki;Takada, Ayato;Kawaoka, Yoshihiro
以埃博拉病毒属和马尔堡病毒属为代表的丝状病毒在人类和非人灵长类动物中引起致死性出血热。虽然丝状病毒可以在这些动物的各种组织或细胞类型中复制，但其广泛嗜性的分子机制仍然知之甚少。在这里，我们显示参与的Tyro 3受体酪氨酸激酶家族的成员- Axl，Dtk，和梅尔-在细胞进入丝状病毒。这些家族成员在淋巴样细胞中的异位表达增强了在其包膜上携带丝状病毒糖蛋白的假型病毒的感染，否则这些淋巴样细胞对丝状病毒感染具有高度抗性。这种增强被Tyro 3家族成员、Gas 6配体或成员的可溶性胞外域的抗体降低。活埃博拉病毒感染Axl和Dtk表达细胞的效率高于对照细胞。Axl抗体抑制假型病毒在Axl阳性细胞系中的感染。这些结果暗示每个Tyro 3家族成员作为丝状病毒感染中的细胞进入因子。
Filoviruses, represented by the genera Ebolavirus and Marburgvirus, cause a lethal hemorrhagic fever in humans and in nonhuman primates. Although filovirus can replicate in various tissues or cell types in these animals, the molecular mechanisms of its broad tropism remain poorly understood. Here we show the involvement of members of the Tyro3 receptor tyrosine kinase family - Axl, Dtk, and Mer-in cell entry of filoviruses. Ectopic expression of these family members in lymphoid cells, which otherwise are highly resistant to filovirus infection, enhanced infection by pseudotype viruses carrying filovirus glycoproteins on their envelopes. This enhancement was reduced by antibodies to Tyro3 family members, Gas6 ligand, or soluble ectodomains of the members. Live Ebola viruses infected both Axl- and Dtk-expressing cells more efficiently than control cells. Antibody to Axl inhibited infection of pseudotype viruses in a number of Axl-positive cell lines. These results implicate each Tyro3 family member as a cell entry factor in filovirus infection.