Janns坦福大学医学院 E. Carette研究小组透露，MFSD6是一种进入受体的肠病毒D68。该研究结果于2025年3月25日在国际顶级学术期刊《自然》上发表。

研究小组成员利用基因组大小的CRISPR筛选，对特征不明确的多通膜转运蛋白MFSD6进行了鉴定，作为EV-D68的宿主进入因子。在细胞系统、呼吸细胞、神经细胞等原代细胞中，通过敲除MFSD6表达可以消除EV-D68的感染。MFSD6定位于质膜上，这是病毒进入宿主细胞所必需的。MFSD6直接通过第三个细胞外环(L3)与EV-D68颗粒结合。研究小组测量了EV-D68和L3在2.1 分辨率，显示交互界面。EV-D68对人类原有肺上皮细胞的感染是通过将MFSD6(L3)装饰成Fc而设计的诱饵受体来阻断的，并且在EV-D68感染的致命motheme模型中提供了几乎完全的保护。总而言之，他们的研究结果表明，MFSD6是EV-D68的一种进入受体，并且支持靶向MFSD6作为一种潜在的新型病原体感染机制，具有很大的流行潜力。

据了解，由于全球疫苗接种运动，脊髓灰质炎病毒几乎被消灭，人们的注意力已经转移到其他肠道病毒主题1-3，可以抑制脊髓灰质炎样麻痹综合征(现称急性松缓性脊髓炎)。尤其是肠道病毒D68 (EV-近年来，D68被认为是AFM流行病爆发的主要驱动因素，但对EV-D68宿主的相互作用却知之甚少。EV-D68是一种呼吸道病毒，但在极少数情况下，它可以扩散到中枢神经系统，引起严重的神经系统疾病。

附：英文原文

Title: MFSD6 is an entry receptor for enterovirus D68

Author: Varanese, Lauren, Xu, Lily, Peters, Christine E., Pintilie, Grigore, Roberts, David S., Raj, Suyash, Liu, Mengying, Ooi, Yaw Shin, Diep, Jonathan, Qiao, Wenjie, Richards, Christopher M., Callaway, Jeremy, Bertozzi, Carolyn R., Jabs, Sabrina, de Vries, Erik, van Kuppeveld, Frank J. M., Nagamine, Claude M., Chiu, Wah, Carette, Jan E.

Issue&Volume: 2025-03-25

Abstract: With the near eradication of poliovirus due to global vaccination campaigns, attention has shifted to other enteroviruses that can cause polio-like paralysis syndrome (now termed acute flaccid myelitis (AFM))1–3. In particular, enterovirus D68 (EV-D68) is believed to be the main driver of epidemic outbreaks of AFM in recent years4, yet not much is known about EV-D68 host interactions. EV-D68 is a respiratory virus5 but, in rare cases, can spread to the central nervous system to cause severe neuropathogenesis. Here, we used genome-scale CRISPR screens to identify the poorly characterized multipass membrane transporter MFSD6 as a host entry factor for EV-D68. Knockout of MFSD6 expression abrogated EV-D68 infection in cell lines and primary cells corresponding to respiratory and neural cells. MFSD6 localized to the plasma membrane and was required for viral entry into host cells. MFSD6 bound directly to EV-D68 particles via its third extracellular loop (L3). We determined the cryo-EM structure of EV-D68 in complex with L3 at 2.1 resolution, revealing the interaction interface. A decoy receptor, engineered by fusing MFSD6(L3) to Fc, blocked EV-D68 infection of human primary lung epithelial cells, and provided near complete protection in a lethal mouse model of EV-D68 infection. Collectively, our results reveal MFSD6 as an entry receptor for EV-D68, and support targeting MFSD6 as a potential mechanism to combat infections by this emerging pathogen with pandemic potential.