一个国际研究小组日前发现，人体细胞内的一种跨膜蛋白在麻疹病毒入侵人体时充当了“内鬼”的角色，为病毒进入细胞敞开大门。这一发现有可能帮助研究人员利用麻疹病毒对抗肿瘤细胞。
麻疹是常见于儿童的急性呼吸道传染病。尽管相关疫苗早已问世，全球目前每年仍有约12万人死于麻疹。麻疹的传染性很强，未接种疫苗者如与麻疹患者接触，其患病几率可超过90％。
通过对麻疹感染机制的多年研究，科研人员已发现麻疹病毒能在特殊受体的协助下进入一些呼吸道细胞，携带该病毒的细胞随后通过淋巴结将麻疹病毒带至各淋巴器官。不过，至于麻疹病毒如何重返呼吸道，此后怎样离开人体、寻找新宿主却难以说清。有学者推测，可能是人体细胞内的某种物质充当了协助麻疹病毒进出人体的“内鬼”。
由德国、美国、加拿大、新加坡和法国研究者组成的一个小组在新一期英国学术周刊《自然》上报告说，为了揪出这一“内鬼”，他们选取肺肿瘤细胞等易受麻疹病毒感染的细胞，研究它们内部是否有一些“与众不同”的蛋白。随后，研究人员将那些可疑蛋白分别放入正常情况下不会感染麻疹病毒的细胞内，看它们会不会有协助麻疹病毒“作案”的异常举动。
经过层层筛查，一种名为Nectin-4的跨膜蛋白终于“暴露身份”。据德国保罗·埃尔利希研究所的米夏埃尔·米勒巴赫博士介绍，Nectin-4跨膜蛋白位于上皮细胞内侧，可接触麻疹病毒并帮助其穿过上皮细胞。研究人员还阻断了指导合成Nectin-4跨膜蛋白的基因表达，结果易感染麻疹病毒的细胞不再感染这种病毒。
不过，研究人员仍不放心，因为他们选取的细胞源自较特殊的肿瘤细胞。为了不“冤枉”Nectin-4跨膜蛋白，研究者又利用正常人的呼吸道上皮细胞进行实验，结果证实Nectin-4跨膜蛋白的确在麻疹病毒进出人体呼吸道时起到了关键作用。
据悉，这一发现不仅有助于麻疹预防研究，而且有望为抗癌研究提供新思路。实际上，麻疹病毒此前已在一些研究中被用作抗癌的“溶瘤病毒”，即利用该病毒自身的不断繁殖杀死肿瘤细胞。不过，这种方法的具体效果还有待进一步检验。(生物谷 Bioon.com)
doi:10.1038/nature10639
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PMID:
Adherens junction protein nectin-4 is the epithelial receptor for measles virus
Michael D. Mühlebach1 Mathieu Mateo2 Patrick L. Sinn3 Steffen Prüfer1 Katharina M. Uhlig1 Vincent H. J. Leonard2 Chanakha K. Navaratnarajah2 Marie Frenzke2 Xiao X. Wong4 Bevan Sawatsky4 Shyam Ramachandran3 Paul B. McCray3 Klaus Cichutek1 Veronika von Messling4, 5 Marc Lopez6 Roberto Cattaneo2
Measles virus is an aerosol-transmitted virus that affects more than 10 million children each year and accounts for approximately 120,000 deaths. Although it was long believed to replicate in the respiratory epithelium before disseminating, it was recently shown to infect initially macrophages and dendritic cells of the airways using signalling lymphocytic activation molecule family member 1 (SLAMF1; also called CD150) as a receptor. These cells then cross the respiratory epithelium and transport the infection to lymphatic organs where measles virus replicates vigorously. How and where the virus crosses back into the airways has remained unknown. On the basis of functional analyses of surface proteins preferentially expressed on virus-permissive human epithelial cell lines, here we identify nectin-4 (ref. ; also called poliovirus-receptor-like-4 (PVRL4)) as a candidate host exit receptor. This adherens junction protein of the immunoglobulin superfamily interacts with the viral attachment protein with high affinity through its membrane-distal domain. Nectin-4 sustains measles virus entry and non-cytopathic lateral spread in well-differentiated primary human airway epithelial sheets infected basolaterally. It is downregulated in infected epithelial cells, including those of macaque tracheae. Although other viruses use receptors to enter hosts or transit through their epithelial barriers, we suggest that measles virus targets nectin-4 to emerge in the airways. Nectin-4 is a cellular marker of several types of cancer, which has implications for ongoing measles-virus-based clinical trials of oncolysis. was measured in treated skin at the peak of UVB-induced hypersensitivity with custom-made
