NRP2 和 CD63 是卢日病毒细胞进入的宿主因素。
NRP2 and CD63 Are Host Factors for Lujo Virus Cell Entry.
机构信息
Division of Biochemistry, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
Division of Biochemistry, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.
出版信息
Cell Host Microbe. 2017 Nov 8;22(5):688-696.e5. doi: 10.1016/j.chom.2017.10.002.
Arenaviruses cause fatal hemorrhagic disease in humans. Old World arenavirus glycoproteins (GPs) mainly engage α-dystroglycan as a cell-surface receptor, while New World arenaviruses hijack transferrin receptor. However, the Lujo virus (LUJV) GP does not cluster with New or Old World arenaviruses. Using a recombinant vesicular stomatitis virus containing LUJV GP as its sole attachment and fusion protein (VSV-LUJV), we demonstrate that infection is independent of known arenavirus receptor genes. A genome-wide haploid genetic screen identified the transmembrane protein neuropilin 2 (NRP2) and tetraspanin CD63 as factors for LUJV GP-mediated infection. LUJV GP binds the N-terminal domain of NRP2, while CD63 stimulates pH-activated LUJV GP-mediated membrane fusion. Overexpression of NRP2 or its N-terminal domain enhances VSV-LUJV infection, and cells lacking NRP2 are deficient in wild-type LUJV infection. These findings uncover this distinct set of host cell entry factors in LUJV infection and are attractive focus points for therapeutic intervention.
沙粒病毒属可导致人类致命性出血热。旧大陆沙粒病毒糖蛋白（GPs）主要通过与细胞表面受体α- 肌动蛋白聚糖结合来感染细胞，而新大陆沙粒病毒则劫持转铁蛋白受体。然而，卢日病毒（LUJV）的 GPs 并不与新世界或旧世界沙粒病毒聚类。本研究使用含有 LUJV GPs 的重组水疱性口炎病毒作为唯一的附着和融合蛋白（VSV-LUJV），证明了感染不依赖于已知的沙粒病毒受体基因。全基因组单倍体遗传筛选鉴定出跨膜蛋白神经纤毛蛋白 2（NRP2）和四跨膜蛋白 CD63 是 LUJV GP 介导感染所必需的因素。LUJV GP 结合 NRP2 的 N 端结构域，而 CD63 则刺激 pH 激活的 LUJV GP 介导的膜融合。NRP2 或其 N 端结构域的过表达增强了 VSV-LUJV 感染，而缺乏 NRP2 的细胞则对野生型 LUJV 感染表现出缺陷。这些发现揭示了 LUJV 感染中这一独特的宿主细胞进入因子集，是治疗干预的有吸引力的焦点。
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