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Lipid Exchange Factors at Membrane Contact Sites in African Swine Fever Virus Infection
African swine fever (ASF) is a hemorrhagic fever of wild and domestic pigs with a high rate of mortality. Originally endemic in Africa, this disease is currently disseminating in Europe and China, causing a large socioeconomic impact. ASF is caused by a DNA virus, African swine fever virus (ASFV). T...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466349/ https://www.ncbi.nlm.nih.gov/pubmed/30813555 http://dx.doi.org/10.3390/v11030199 |
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author | Galindo, Inmaculada Cuesta-Geijo, Miguel Ángel del Puerto, Ana Soriano, Eva Alonso, Covadonga |
author_facet | Galindo, Inmaculada Cuesta-Geijo, Miguel Ángel del Puerto, Ana Soriano, Eva Alonso, Covadonga |
author_sort | Galindo, Inmaculada |
collection | PubMed |
description | African swine fever (ASF) is a hemorrhagic fever of wild and domestic pigs with a high rate of mortality. Originally endemic in Africa, this disease is currently disseminating in Europe and China, causing a large socioeconomic impact. ASF is caused by a DNA virus, African swine fever virus (ASFV). There is no vaccine available against ASFV, limiting the options for disease control. ASFV reorganizes intracellular membranes to generate viral factories (VFs) in order to amplify its genome. However, little is known about the process involved in the formation of these viral replication organelles. Membrane contact sites (MCSs) allow nonvesicular lipids and ion exchange between organelles. Lipid exchange to form VFs apparently requires a number of proteins at MCSs, such as the oxysterol-binding protein (OSBP), the acyl-coenzyme A binding domain containing 3 (ACBD3) and the phosphatidylinositol-phosphate-4-kinase III beta (PI4Kβ). Itraconazole (ITZ) is an antifungal agent that targets sterol-transport molecules such as OSBP and OSBP-related protein 4 (ORP4). 25-Hydroxycholesterol (25-HC) inhibits lipid transport by high affinity binding OSBP. In this work, we analyzed the antiviral function of ITZ and 25-HC against ASFV in Vero cell cultures using the cell-adapted Ba71V isolate. ITZ and 25-HC decreased significantly ASFV replication. Our study revealed OSBP distribution in cytoplasmic membranes in uninfected Vero cells and to the periphery of VFs in infected cells. In addition, we showed that OSBP and OSBP-related proteins, PI4Kβ and ACBD3 were recruited to VFs in the context ASFV infection. |
format | Online Article Text |
id | pubmed-6466349 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-64663492019-04-18 Lipid Exchange Factors at Membrane Contact Sites in African Swine Fever Virus Infection Galindo, Inmaculada Cuesta-Geijo, Miguel Ángel del Puerto, Ana Soriano, Eva Alonso, Covadonga Viruses Article African swine fever (ASF) is a hemorrhagic fever of wild and domestic pigs with a high rate of mortality. Originally endemic in Africa, this disease is currently disseminating in Europe and China, causing a large socioeconomic impact. ASF is caused by a DNA virus, African swine fever virus (ASFV). There is no vaccine available against ASFV, limiting the options for disease control. ASFV reorganizes intracellular membranes to generate viral factories (VFs) in order to amplify its genome. However, little is known about the process involved in the formation of these viral replication organelles. Membrane contact sites (MCSs) allow nonvesicular lipids and ion exchange between organelles. Lipid exchange to form VFs apparently requires a number of proteins at MCSs, such as the oxysterol-binding protein (OSBP), the acyl-coenzyme A binding domain containing 3 (ACBD3) and the phosphatidylinositol-phosphate-4-kinase III beta (PI4Kβ). Itraconazole (ITZ) is an antifungal agent that targets sterol-transport molecules such as OSBP and OSBP-related protein 4 (ORP4). 25-Hydroxycholesterol (25-HC) inhibits lipid transport by high affinity binding OSBP. In this work, we analyzed the antiviral function of ITZ and 25-HC against ASFV in Vero cell cultures using the cell-adapted Ba71V isolate. ITZ and 25-HC decreased significantly ASFV replication. Our study revealed OSBP distribution in cytoplasmic membranes in uninfected Vero cells and to the periphery of VFs in infected cells. In addition, we showed that OSBP and OSBP-related proteins, PI4Kβ and ACBD3 were recruited to VFs in the context ASFV infection. MDPI 2019-02-26 /pmc/articles/PMC6466349/ /pubmed/30813555 http://dx.doi.org/10.3390/v11030199 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Galindo, Inmaculada Cuesta-Geijo, Miguel Ángel del Puerto, Ana Soriano, Eva Alonso, Covadonga Lipid Exchange Factors at Membrane Contact Sites in African Swine Fever Virus Infection |
title | Lipid Exchange Factors at Membrane Contact Sites in African Swine Fever Virus Infection |
title_full | Lipid Exchange Factors at Membrane Contact Sites in African Swine Fever Virus Infection |
title_fullStr | Lipid Exchange Factors at Membrane Contact Sites in African Swine Fever Virus Infection |
title_full_unstemmed | Lipid Exchange Factors at Membrane Contact Sites in African Swine Fever Virus Infection |
title_short | Lipid Exchange Factors at Membrane Contact Sites in African Swine Fever Virus Infection |
title_sort | lipid exchange factors at membrane contact sites in african swine fever virus infection |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466349/ https://www.ncbi.nlm.nih.gov/pubmed/30813555 http://dx.doi.org/10.3390/v11030199 |
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