Abstract
Prions are proteins that can fold into multiple conformations some of which are self-propagating. Such prion-forming proteins have been found in animal, plant, fungal and bacterial species, but have not yet been identified in viruses. Here we report that LEF-10, a baculovirus-encoded protein, behaves as a prion. Full-length LEF-10 or its candidate prion-forming domain (cPrD) can functionally replace the PrD of Sup35, a widely studied prion-forming protein from yeast, displaying a [PSI+]-like phenotype. Furthermore, we observe that high multiplicity of infection can induce the conversion of LEF-10 into an aggregated state in virus-infected cells, resulting in the inhibition of viral late gene expression. Our findings extend the knowledge of current prion proteins from cellular organisms to non-cellular life forms and provide evidence to support the hypothesis that prion-forming proteins are a widespread phenomenon in nature.
Highlights
Prions are proteins that can fold into multiple conformations some of which are selfpropagating
The sensor system comprises a LEF-10-EGFP driven by the native lef-10 promoter and an mCherry reporter regulated by a baculovirus very late promoter (Fig. 1a and Supplementary Fig. 1e)
In our designed genetic sensor system, correlation of the LEF-10-EGFP state with its regulated mCherry readout implied that aggregation of LEF-10 limited the availability of the fusion protein to activate the Autographa californica multiple nucleopolyhedrovirus (AcMNPV) late promoter thereby reducing the expression of the mCherry reporter
Summary
Prions are proteins that can fold into multiple conformations some of which are selfpropagating. Luminidependens (LD), the first identified plant protein behaving as a prion, is a transcriptional regulator involved in the vernalization[11,17] Such a selfpropagating conformational change in LD is considered to be a signal that can switch plants between reproductive and vegetative growth[11]. This suggests that prion-like conversion can act as a sensor, responding to environmental change, and subsequently regulate gene expression and cellular processes. Prion-like conformation of mitochondrial antiviral signaling protein (MAVS) and the apoptosis-associated protein ASC in mammalian cells activate the downstream immunological or inflammatory signaling pathways[20,21] These findings suggest that the ability to switch a protein to a heritable prion form under certain conditions may offer the host evolutionary advantages. The potential evolutionary advantage suggests that prion proteins should exist widely in various types of organisms
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