Entry of bunyaviruses into mammalian cells.

Entry of bunyaviruses into mammalian cells.
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DOI:
10.1016/j.chom.2010.05.007
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发表时间:
2010-06-25
影响因子:
30.3
通讯作者:
Helenius A
Helenius A
中科院分区:
医学1区
文献类型:
--
作者:
Lozach PY;Mancini R;Bitto D;Meier R;Oestereich L;Overby AK;Pettersson RF;Helenius A

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布尼亚病毒科是一个大家族的有包膜动物病毒,其中许多成员造成严重的疾病。然而,早期布尼亚病毒-宿主细胞相互作用和进入机制仍然在很大程度上未被表征。调查Uukuniemi病毒,白蛉病毒属的布尼亚病毒,我们发现,病毒附着到细胞表面是特异性的,但效率低下,与25%的结合的病毒被内吞在10分钟内,主要是通过非包被囊泡。病毒进入Rab 5a+早期内体,随后进入Rab 7a+和LAMP-1+晚期内体。在内化后20-40分钟发生的酸活化渗透需要早期至晚期内体的成熟。病毒膜融合的pH阈值为5.4,并且进入对低于25°C的温度敏感。总之,我们的研究结果表明,Uukuniemi病毒穿透宿主细胞的酸激活膜融合从晚期内体隔室。这项研究还强调了内吞途径的降解分支在促进晚期穿透病毒进入中的重要性。Uukuniemi本扬病毒的内吞作用主要是不依赖网格蛋白的。摄取后,病毒颗粒通过早期至晚期内体进行。病毒穿透通过晚期内体的酸活化膜融合发生。
The Bunyaviridae constitute a large family of enveloped animal viruses, many members of which cause serious diseases. However, early bunyavirus-host cell interactions and entry mechanisms remain largely uncharacterized. Investigating Uukuniemi virus, a bunyavirus of the genus Phlebovirus, we found that virus attachment to the cell surface was specific but inefficient, with 25% of bound viruses being endocytosed within 10 min, mainly via noncoated vesicles. The viruses entered Rab5a+ early endosomes and, subsequently, Rab7a+ and LAMP-1+ late endosomes. Acid-activated penetration, occurring 20–40 min after internalization, required maturation of early to late endosomes. The pH threshold for viral membrane fusion was 5.4, and entry was sensitive to temperatures below 25°C. Together, our results indicate that Uukuniemi virus penetrates host cells by acid-activated membrane fusion from late endosomal compartments. This study also highlights the importance of the degradative branch of the endocytic pathway in facilitating entry of late-penetrating viruses. ► Endocytosis of the bunyavirus Uukuniemi is mainly clathrin independent ► After uptake, the virus particles are routed via early to late endosomes ► Virus penetration occurs by acid-activated membrane fusion from late endosomes
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