Abstract
African swine fever virus (ASFV) infectious cycle starts with the viral adsorption and entry into the host cell. Then, the virus is internalized via clathrin/dynamin mediated endocytosis and macropinocytosis. Similar to other viruses, ASF virion is then internalized and incorporated into the endocytic pathway. While the endosomal maturation entails luminal acidification, the decrease in pH acts on the multilayer structure of the virion dissolving the outer capsid. Upon decapsidation, the inner viral membrane is exposed to interact with the limiting membrane of the late endosome for fusion. Viral fusion is then necessary for the egress of incoming virions from endosomes into the cytoplasm, however this remains an intriguing and yet essential process for infection, specifically for the egress of viral nucleic acid into the cytoplasm for replication. ASFV proteins E248R and E199L, located at the exposed inner viral membrane, might be implicated in the fusion step. An interaction between these viral proteins and cellular endosomal proteins such as the Niemann-Pick C type 1 (NPC1) and lysosomal membrane proteins (Lamp-1 and -2) was shown. Furthermore, the silencing of these proteins impaired ASFV infection. It was also observed that NPC1 knock-out cells using CRISPR jeopardized ASFV infection and that the progression and endosomal exit of viral cores was arrested within endosomes at viral entry. These results suggest that the interactions of ASFV proteins with some endosomal proteins might be important for the membrane fusion step. In addition to this, reductions on ASFV infectivity and replication in NPC1 KO cells were accompanied by fewer and smaller viral factories. Our findings pave the way to understanding the role of proteins of the endosomal membrane in ASFV infection.
Highlights
African Swine Fever Virus (ASFV) is the only known member of the Asfarviridae family, and the only known DNA arbovirus
African swine fever virus (ASFV) causes a deadly disease of pigs and wild boars that was endemic in Africa but has spread in recent years to Europe, Asia and Oceania with a high socioeconomic impact
To further study the effect of this on ASFV infection, we explored whether there was a correlation between cholesterol retention and reduced ASFV infectivity at the same drug concentrations
Summary
African Swine Fever Virus (ASFV) is the only known member of the Asfarviridae family, and the only known DNA arbovirus. It is a large, enveloped virus with an average diameter of 200 nm and a multilayered structure and icosahedral morphology that has been recently unveiled in detail [1–3]. ASFV is the causative agent of the high mortality haemorrhagic disease affecting swine that is endemic in sub-Saharan Africa. ASF epidemics that started in the Caucasus and Russian Federation in 2007 [4], have rapidly spread to different countries in Europe, Asia and Oceania; causing a devastating burden on the global pig industry [5]. After attachment to an unknown receptor, the virus is mainly internalized via clathrin/dynamin mediated endocytosis and macropinocytosis [10,11]. The virion is internalized and incorporated into the endocytic pathway
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