On July 15, 2019, Cell published a research article titled "Human neonatal Fc receptor is the cellular uncoating receptor for Enterovirus B" jointly contributed by Wensheng Wei’s group from Peking University, George Fu Gao’s group from Institute of Microbiology, Chinese Academy of Sciences, and Zhengde Xie’s group from Beijing Children’s hospital, reporting that human neonatal Fc receptor (FcRn) is the uncoating receptor for major EV-B and the underlying mechanisms by which FcRn mediates viral entry.

Enteroviruses are positive-sense single-stranded RNA viruses. The common enterovirus includes poliovirus that causes poliomyelitis, as well as EV-71, EV-D68, and CV-A6 that cause hand-foot-and-mouth disease in children. Echovirus infection could lead to encephalitis/meningitis in children. To date, no vaccine, drugs, and animal models are available for the echovirus treatment and research, and the host receptor responsible for viral entry remains elusive. In collaboration with George Fu Gao’s and Zhengde Xie’s groups, Wensheng Wei’s group identified FcRn as the cellular receptor for EV-B by genome-wide CRISPR screening.

Figure 1. Schematic diagram of Echo 6 receptor screening

It is known that FcRn facilitates the transport of maternal IgG across the placenta to the fetus and across the intestinal epithelium to the bloodstream of the newborn, as well as mediating the recycling of IgG for adults. By genetics and biochemistry approaches, together with the cryogenic electron microscopy for structure determination, FcRn is verified to be exploited by a large group of EV-B viruses for entry into the cell. Moreover, the molecular mechanism of action by which FcRn mediates EV-B virus entry is elucidated.

Figure 2. FcRn is the receptor of a large group of EV-B viruses

This study provided insights and tools for echovirus research, including 1) helped to understand how echovirus penetrates blood-brain barrier to cause diseases such as encephalitis, 2) provided an animal disease model for echovirus, which is important for the evaluation of candidate vaccines and drugs, and 3) provided the basis for the engineering of the therapeutic virus, as echovirus has been leveraged as the oncolytic virus for treating cancers in countries such as Latvija, while how to improve the specificity of killing is challenging. Overall, this study provided valuable information for both basic and clinical research.

Figure 3. Model of Echovirus Entry into the Cell

Dr. Xin Zhao (George Fu Gao group), Dr. Guigen Zhang (Wensheng Wei group), Sheng Liu (George Fu Gao group), and Dr. Xiangpeng Chen (Zhengde Xie group) are the co-first authors of the paper. Prof. George Fu Gao, Prof. Wensheng Wei, and Prof. Zhengde Xie are the co-corresponding authors. This project is supported by funds from the National Science Foundation of China, the Beijing Advanced Innovation Center for Genomics at Peking University, the Peking-Tsinghua Center for Life Sciences, and the Beijing Municipal Science & Technology Commission.

Article link: https://www.cell.com/action/showPdf?pii=S0092-8674(19)30454-4