Hijacking host extracellular vesicle machinery by hepatotropic viruses: current understandings and future prospects

Table 1 Summary of current understanding in the host vesicular machinery utilized by exosomal hepatotropic viruses

	eHAV	eHBV	eHCV	eHDV	eHEV
Receptor	HAVCR1 (TIM-1), NPC1, and disialogangliosides [81, 82]	NTCP [97]	Unknown or no need (directly fusogenic) [115, 117]	Unknown	HAVCR1 (TIM-1) [151]
Protein marker	Phosphatidylserine, CD9, CHMP2A, and DPP4 [76, 82]	CD63, CD81 and LHBs [94,95,96,97]	CD81, CD63, TSG101, VPS4B, CHAMP4B, and HCV E2 protein [115,116,117, 120]	CD63, TSG101, and CD81 [137]	Phosphatidylserine, sphingomyelin, ceramides, cholesterol, TSG101, HRS, VPS4A, VPS4B, HEV ORF3 [142, 146, 147, 151]
Clathrin- and dynamin-dependent endocytosis	Yes [77]	Yes [87]	Employed by canonical HCV entry, but unknown for eHCV	Unknown	Yes [148, 150]
ESCRT utilization	VPS4B, ALIX, CHMP2A and PTPN23 [75, 79]	ALIX, and VPS4B used by canonical HBV replication [89, 90]	HRS, syntenin, ALIX, TSG101, VPS4B, CHAMP4B [116, 120]	TSG101 [137]	HRS, TSG101, VPS4A, VPS4B [146]
nSMase/ceramide utilization	Unknown	Yes [94, 97]	Yes [117, 121]	Unknown	Yes [146]
Rab GTPase utilization	Rab5C and Rab7A regulate eHAV biogenesis and secretion [76]	Rab5, Rab7, and Rab33B used by canonical HBV replication [88, 91, 92]	Rab5, Rab7, Rab9, and Rab27A employed by both canonical HCV replication and eHCV biogenesis [103, 104, 108, 111, 121]	Unknown	Rab27A for release [146], and Rab5 and Rab7 for entry [148]
Viral factor required for exosomal virus	pX [78]	Unknown	HCV E2 protein [120]	Unknown	HEV ORF2 and ORF3 [146]
Clinical evidence	Yes [75]	Yes [95]	Yes [115, 119, 120]	Unknown	Yes [144]

eHAV exosomal HAV or quasi-enveloped HAV, eHBV exosomal HBV, eHCV exosomal HCV, eHDV exosomal HDV, eHEV exosomal HEV or quasi-enveloped HEV

ISSN: 1423-0127