African Swine Fever Virus Gets Undressed: New Insights on the Entry Pathway

Abstract

African swine fever virus (ASFV) is a large, multienveloped DNA virus composed of a genome-containing core successively wrapped by an inner lipid envelope, an icosahedral protein capsid, and an outer lipid envelope. In keeping with this structural complexity, recent studies have revealed an intricate entry program. This Gem highlights how ASFV uses two alternative pathways, macropinocytosis and clathrin-mediated endocytosis, to enter into the host macrophage and how the endocytosed particles undergo a stepwise, low pH-driven disassembly leading to inner envelope fusion and core delivery in the cytoplasm.

Keywords: African swine fever virus; virus entry; virus membrane fusion; virus uncoating.

FIG 1

Working model for ASFV entry and uncoating. (A) ASFV can enter swine macrophages by clathrin-mediated endocytosis and actin-driven macropinocytosis. Once endocytosed, incoming particles transit from early endosomes and macropinosomes to late multivesicular endosomes, where they undergo a low pH-driven, stepwise disassembly process. It involves disruption of the capsid (light blue), dissociation of the outer membrane (purple), and fusion of the inner viral envelope (pink) with the limiting endosomal membrane (dark blue). As a consequence, naked cores are delivered into the cytosol, where they presumably undergo further uncoating to release replication-competent genomes. Membrane fusion and core delivery depend on inner envelope protein pE248R. Electron micrographs illustrate clathrin-mediated endocytosis (B) and macropinocytosis (C) of extracellular ASFV particles, an intact virion within an early endosome (D) a disrupted particle (without capsid and with a fragmented, partially detached outer envelope) within a late endosome (E), and a cytosolic naked core (F). Bars, 100 nm.