New insights into the role of endosomal proteins for African swine fever virus infection

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 socio-economic impact. ASFV enters the cell by endocytosis and has adapted to the endosomal conditions to acquire infectivity. Fusion of the internal viral membrane with the endosomal membrane is required for the exit of viral DNA into the cytoplasm to start replication. We have found that ASF virion internal membrane proteins E248R and E199L interact with the endosomal proteins Niemann Pick C1 (NPC1) and lysosomal membrane protein (Lamp)-1 and -2. And, appear to be required for endosomal trafficking of ASF virions endosomal traffic and exit to the cytoplasm in the cell entry process. These molecules act regulating cholesterol flux from the endosome to the endoplasmic reticulum and appear to be important for the viral infection cycle. In silenced and knockout cells, ASFV infection was affected at early and later stages. In null cells, virion entry and progression through the endosomal pathway at entry were arrested and several viral cores were retained at late endosomes without entering the fusion phase for the cytoplasmic exit. These results provide new insights into the role of endosomal proteins for ASFV infection