Lipid Exchange Factors at Membrane Contact Sites in African Swine Fever Virus Infection.

Abstract

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.

• Authors: Inmaculada Galindo, Miguel Ángel Cuesta-Geijo, Ana Del Puerto, Eva Soriano, Covadonga Alonso
• Journal: Viruses (Viruses) Vol. 11 Issue 3 (02 26 2019) ISSN: 1999-4915 [Electronic] Switzerland
• PMID: 30813555 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ACBD3 protein, human
• Adaptor Proteins, Signal Transducing
• Antiviral Agents
• Hydroxycholesterols
• Membrane Proteins
• Minor Histocompatibility Antigens
• Receptors, Steroid
• oxysterol binding protein
• Itraconazole
• 25-hydroxycholesterol
• Phosphotransferases (Alcohol Group Acceptor)
• phosphatidylinositol phosphate 4-kinase

Topics

• Adaptor Proteins, Signal Transducing (genetics)
• African Swine Fever
• African Swine Fever Virus (drug effects, metabolism)
• Animals
• Antiviral Agents (pharmacology)
• Chlorocebus aethiops
• Genome, Viral
• HeLa Cells
• Host Microbial Interactions
• Humans
• Hydroxycholesterols (pharmacology)
• Itraconazole (pharmacology)
• Lipid Metabolism
• Membrane Proteins (genetics)
• Minor Histocompatibility Antigens (genetics)
• Phosphotransferases (Alcohol Group Acceptor) (genetics)
• Receptors, Steroid (drug effects)
• Swine
• Vero Cells
• Virus Attachment