Abstract
Every year, there are about 20 Mio hepatitis E virus (HEV) infections and 60,000 deaths that are associated with HEV worldwide. At the present, there exists no specific therapy for HEV. The natural compound silvestrol has a potent antiviral effect against the (−)-strand RNA-virus Ebola virus, and also against the (+)-strand RNA viruses Corona-, Picorna-, and Zika virus. The inhibitory effect on virus spread is due to an inhibition of the DEAD-box RNA helicase eIF4A, which is required to unwind structured 5′-untranslated regions (UTRs). This leads to an impaired translation of viral RNA. The HEV (+)-strand RNA genome contains a 5′-capped, short 5′-UTR. This study aims to analyze the impact of silvestrol on the HEV life cycle. Persistently infected A549 cells were instrumental. This study identifies silvestrol as a potent inhibitor of the release of HEV infectious viral particles. This goes along with a strongly reduced HEV capsid protein translation, retention of viral RNA inside the cytoplasm, and without major cytotoxic effects. Interestingly, in parallel silvestrol affects the activity of the antiviral major vault protein (MVP) by translocation from the cytoplasm to the perinuclear membrane. These data further characterize the complex antiviral activity of silvestrol and show silvestrol’s broad spectrum of function, since HEV is a virus without complex secondary structures in its genome, but it is still affected.
Highlights
The Hepatitis E Virus, which was first discovered in 1980 [1], is one of the major causes of an acute hepatitis worldwide, most often spreading in developing countries with poor hygiene standards, hepatitis E virus (HEV) immune responses can be observed all over the world [2].Especially in recent years, since more case studies and controls have been conducted, it has been observed that HEV is widespread in European countries [3] and in the Americas [4,5]
The aim of this study is to evaluate the possible antiviral effects of silvestrol on HEV, thereby getting deeper insights in the virus’ life cycle and to further characterize silvestrol with respect to its antiviral activity, possibly identifying novel host-factors being important in the context of HEV-infection besides eukaryotic initiation factor 4A (eIF4A)
To study the potential antiviral effect of silvestrol on HEV, HEV, persistently HEV-infected A549 cells were treated with silvestrol and the number number of of released released HEV
Summary
In recent years, since more case studies and controls have been conducted, it has been observed that HEV is widespread in European countries [3] and in the Americas [4,5]. Since this topic has become more aware, it became obvious that HEV is a virus that is considered to be water-borne, and food-borne [6]. Meat-consuming customers in Western countries are at risk of HEV
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