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.
Copyright: © 2023 Yu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.