EBioMedicine · 2025
Characterisation of a secreted MFSD6-Fc microbody as a decoy receptor for respiratory enterovirus D68.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Li Zhaoxue, Li Huili, Liu Xize, Zhou Junfeng, Gao Delong, Yang Wanying, Xia Huiming, Dou Chao, Yu Zhenglei, Guo Haoran, Wei Wei
Аннотация
BACKGROUND: Enterovirus D68 (EV-D68) is a prominent non-polio enterovirus known to cause severe respiratory infections and poliomyelitis-like illnesses in children. Recently, we identified MFSD6 as a receptor for EV-D68, providing a potential target for blocking viral entry into cells. This study aimed to develop an MFSD6-based decoy receptor to neutralise EV-D68 and elucidate its mechanism of action.
METHODS: In this study, we engineered a secreted MFSD6-Fc microbody (secMFSD6 Mb) and evaluated its efficacy using in vitro binding assays (co-immunoprecipitation, RT-qPCR), electron microscopy, and functional studies in EV-D68-infected respiratory cell lines (Calu-3, BEAS-2B, A549), primary human bronchial epithelial cells (HBECs), and a neonatal ICR mouse model (n = 9 per group) infected with EV-D68. Statistical significance was determined by two-way ANOVA and t-test (GraphPad Prism 8.0.2; significance threshold P < 0.05).
FINDINGS: secMFSD6 Mb occupies the receptor-binding sites on the viral surface, reducing virus attachment to cells by >90% (n = 3 biological replicates). Electron microscopy showed conversion of intact virions to empty capsids after Mb treatment, and sucrose-gradient analysis demonstrated a 6-fold increase in free viral RNA (F2 fraction) compared with control. In mice challenged with 1 × 107 TCID50 of US/MO/14-18947, secMFSD6 Mb increased 15-day survival from 11% (1/9) to 89% (8/9).
INTERPRETATION: This decoy receptor strategy may support the development of effective therapeutic approaches against EV-D68 infection.
FUNDING: HYPNSFC Excellent Young Scientist Fund (32222005), the National Natural Science Foundation of China (82372226, 82172246), the National Major Project for Infectious Disease Control and Prevention (2018ZX10731-101-001-016).
METHODS: In this study, we engineered a secreted MFSD6-Fc microbody (secMFSD6 Mb) and evaluated its efficacy using in vitro binding assays (co-immunoprecipitation, RT-qPCR), electron microscopy, and functional studies in EV-D68-infected respiratory cell lines (Calu-3, BEAS-2B, A549), primary human bronchial epithelial cells (HBECs), and a neonatal ICR mouse model (n = 9 per group) infected with EV-D68. Statistical significance was determined by two-way ANOVA and t-test (GraphPad Prism 8.0.2; significance threshold P < 0.05).
FINDINGS: secMFSD6 Mb occupies the receptor-binding sites on the viral surface, reducing virus attachment to cells by >90% (n = 3 biological replicates). Electron microscopy showed conversion of intact virions to empty capsids after Mb treatment, and sucrose-gradient analysis demonstrated a 6-fold increase in free viral RNA (F2 fraction) compared with control. In mice challenged with 1 × 107 TCID50 of US/MO/14-18947, secMFSD6 Mb increased 15-day survival from 11% (1/9) to 89% (8/9).
INTERPRETATION: This decoy receptor strategy may support the development of effective therapeutic approaches against EV-D68 infection.
FUNDING: HYPNSFC Excellent Young Scientist Fund (32222005), the National Natural Science Foundation of China (82372226, 82172246), the National Major Project for Infectious Disease Control and Prevention (2018ZX10731-101-001-016).