التفاصيل البيبلوغرافية
| العنوان: |
New insights into the role of endosomal proteins for African swine fever virus infection. |
| المؤلفون: |
Cuesta-Geijo, Miguel Ángel, García-Dorival, Isabel, del Puerto, Ana, Urquiza, Jesús, Galindo, Inmaculada, Barrado-Gil, Lucía, Lasala, Fátima, Cayuela, Ana, Sorzano, Carlos Oscar S., Gil, Carmen, Delgado, Rafael, Alonso, Covadonga |
| المصدر: |
PLoS Pathogens; 1/26/2022, Vol. 18 Issue 1, p1-28, 28p |
| مصطلحات موضوعية: |
AFRICAN swine fever virus, AFRICAN swine fever, VIRUS diseases, MEMBRANE proteins, MEMBRANE fusion, VIRAL proteins |
| مصطلحات جغرافية: |
OCEANIA |
| مستخلص: |
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. Similarly, 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. Author summary: 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. 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 was arrested and several viral cores were retained at late endosomes without entering the fusion phase for cytoplasmic exit. These results provide new insights into the role of endosomal proteins for ASFV infection. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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