The lifecycle of the Ebola virus in host cells

Abstract

Ebola haemorrhagic fever causes deadly disease in humans and non-human primates resulting from infection with the Ebola virus (EBOV) genus of the family Filoviridae. However, the mechanisms of EBOV lifecycle in host cells, including viral entry, membrane fusion, RNP formation, GP-tetherin interaction, and VP40-inner leaflet association remain poorly understood. This review describes the biological functions of EBOV proteins and their roles in the lifecycle, summarizes the factors related to EBOV proteins or RNA expression throughout the different phases, and reviews advances with regards to the molecular events and mechanisms of the EBOV lifecycle. Furthermore, the review outlines the aspects remain unclear that urgently need to be solved in future research.

Keywords: EBOV lifecycle; EBOV proteins; Ebola virus.

Figure 1. EBOV genome

The genes are depicted as boxes: nucleoprotein (NP), viral protein (VP) 35, matrix protein VP40, glycoprotein (GP), VP30, VP24, and polymerase protein (L).

Figure 2. EBOV lifecycle

Entry: EBOV enters cells via binding to receptors or co-receptors, in the macropinocytosis pathway, although debate still exists. Uncoating and fusion: In the endosome, proteolytic cleavage, and other unknown factors trigger uncoating of nucleocapsids; NPC1 induces the fusion of EBOV and cellular membranes. Transcription and replication: Viral mRNA is transcribed via the viral polymerase, and the viral proteins are subsequently translated. Replication of the viral genome is present in the form of RNP. The molecular mechanism of RNP and the mechanism by which VP35 releases RNA from RNP remain unknown. Assembly and budding: Assembly is initiated by the nucleocapsids which accumulate in the perinuclear region, and are then transported to the budding sites at the plasma membrane. Budding: Occurs at the plasma membrane, intracellular membranes of the MVBs and late endosomes. VP40 and GP play critical roles in the budding process. Abbreviations: ER: endoplasmic reticulum; MVB: multivesicular body; NPC1: Niemann-Pick C1.