African swine fever virus-cell interactions: From virus entry to cell survival

Viruses have adapted to evolve complex and dynamic interactions with their host cell. The viral entry mechanism determines viral tropism and pathogenesis. The entry of African swine fever virus (ASFV) is dynamin-dependent and clathrin-mediated, but other pathways have been described such as macropinocytosis. During endocytosis, ASFV viral particles undergo disassembly in various compartments that the virus passes through en route to the site of replication. This disassembly relies on the acid pH of late endosomes and on microtubule cytoskeleton transport. ASFV interacts with several regulatory pathways to establish an optimal environment for replication. Examples of these pathways include small GTPases, actin-related signaling, and lipid signaling. Cellular cholesterol, the entire cholesterol biosynthesis pathway, and phosphoinositides are central molecular networks required for successful infection. Here we report new data on the conformation of the viral replication site or viral factory and the remodeling of the subcellular structures. We review the virus-induced regulation of ER stress, apoptosis and autophagy as key mechanisms of cell survival and determinants of infection outcome. Finally, future challenges for the development of new preventive strategies against this virus are proposed on the basis of current knowledge about ASFV-host interactions.

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► ASFV entry by dynamin-dependent and clathrin-mediated endocytosis or macropinocytosis.
► Endosomal maturation, Rab7 GTPase and acidification of late endosomes are required for virus desencapsidation.
► ASFV regulates ER stress and unfolded protein response.
► Inhibition of apoptosis or cytoplasmic membrane blebbing impair virus exit.
► ASFV regulates autophagy by ASFV Bcl2 interaction with Beclin1.