Engineering Center of Agricultural Biosafety Assessment and Biotechnology, School of Advanced Agricultural Sciences, Yibin Vocational and Technical College, Yibin, People's Republic of China.
Nanchong Key Laboratory of Disease Prevention, Control and Detection in Livestock and Poultry, Nanchong Vocational and Technical College, Nanchong, People's Republic of China.
PLoS Pathog. 2023 Sep 14;19(9):e1011619. doi: 10.1371/journal.ppat.1011619. eCollection 2023 Sep.
The host cell membrane-associated RING-CH 8 protein (MARCH8), a member of the E3 ubiquitin ligase family, regulates intracellular turnover of many transmembrane proteins and shows potent antiviral activities. Generally, 2 antiviral modes are performed by MARCH8. On the one hand, MARCH8 catalyzes viral envelope glycoproteins (VEGs) ubiquitination and thus leads to their intracellular degradation, which is the cytoplasmic tail (CT)-dependent (CTD) mode. On the other hand, MARCH8 traps VEGs at some intracellular compartments (such as the trans-Golgi network, TGN) but without inducing their degradation, which is the cytoplasmic tail-independent (CTI) mode, by which MARCH8 hijacks furin, a cellular proprotein convertase, to block VEGs cleavage. In addition, the MARCH8 C-terminal tyrosine-based motif (TBM) 222YxxL225 also plays a key role in its CTI antiviral effects. In contrast to its antiviral potency, MARCH8 is occasionally hijacked by some viruses and bacteria to enhance their invasion, indicating a duplex role of MARCH8 in host pathogenic infections. This review summarizes MARCH8's antiviral roles and how viruses evade its restriction, shedding light on novel antiviral therapeutic avenues.
宿主细胞膜相关的 RING-CH 8 蛋白（MARCH8），E3 泛素连接酶家族的一员，调节许多跨膜蛋白的细胞内周转，并显示出强大的抗病毒活性。通常，MARCH8 通过两种抗病毒模式发挥作用。一方面，MARCH8 催化病毒包膜糖蛋白（VEGs）的泛素化，从而导致其在细胞内降解，这是细胞质尾巴（CT）依赖性（CTD）模式。另一方面，MARCH8 将 VEGs 困在一些细胞内隔室（如高尔基体、TGN）中，但不诱导其降解，这是细胞质尾巴非依赖性（CTI）模式，通过这种模式，MARCH8 劫持了细胞蛋白转化酶 furin，阻止 VEGs 的切割。此外，MARCH8 的 C 端酪氨酸基基序（TBM）222YxxL225 也在其 CTI 抗病毒作用中发挥关键作用。与它的抗病毒效力相反，MARCH8 偶尔会被一些病毒和细菌劫持，以增强它们的入侵，表明 MARCH8 在宿主致病性感染中具有双重作用。这篇综述总结了 MARCH8 的抗病毒作用以及病毒如何逃避其限制，为新的抗病毒治疗途径提供了线索。
