Cuesta-Geijo, Miguel Angel, Garcia-Dorival, Isabel 
ORCID: 0000-0002-5654-5662, del Puerto, Ana, Urquiza, Jesus, Galindo, Inmaculada, Barrado-Gil, Lucia, Lasala, Fatima, Cayuela, Ana, Sorzano, Carlos Oscar S, Gil, Carmen et al (show 2 more authors)
(2022)
New insights into the role of endosomal proteins for African swine fever virus infection.
PLOS PATHOGENS, 18 (1).
e1009784-.
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Vero Cells, Endosomes, Animals, Swine, Humans, African Swine Fever Virus, African Swine Fever, Viral Proteins, Host-Pathogen Interactions, HEK293 Cells, Chlorocebus aethiops |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 11 May 2022 09:19 |
| Last Modified: | 18 Jan 2023 21:03 |
| DOI: | 10.1371/journal.ppat.1009784 |
| Open Access URL: | https://doi.org/10.1371/journal.ppat.1009784 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3154601 |
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