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

Inmaculada Galindo,Ana Del Puerto,Covadonga Alonso,Miguel Cuesta-Geijo,Eva Soriano

doi:10.3390/v11030199

Inmaculada Galindo, Ana Del Puerto + Show 3 more

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https://doi.org/10.3390/v11030199

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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.

Highlights

African swine fever virus (ASFV) causes a highly contagious disease affecting wild and domestic pigs
African Swine Fever (ASF) causes severe economic losses for pig industry due to the high rate of mortality associated with the illness and the difficulties to control the disease in the absence of an effective vaccine [1,2]
Our results showed that ASFV infection induced changes in oxysterol-binding protein (OSBP) pattern in Vero cells at 16 hpi

Summary

Introduction

African swine fever virus (ASFV) causes a highly contagious disease affecting wild and domestic pigs. African Swine Fever (ASF) causes severe economic losses for pig industry due to the high rate of mortality associated with the illness and the difficulties to control the disease in the absence of an effective vaccine [1,2]. ASFV is the only member of the Asfarviridae family [1]. It is an enveloped virus with icosahedral morphology and an average diameter of 200 nm. It requires the nucleus for viral DNA synthesis at early times [8,9]

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