Abstract
ABSTRACTAfrican swine fever virus (ASFV) infection is characterized by a progressive decrease in cellular protein synthesis with a concomitant increase in viral protein synthesis, though the mechanism by which the virus achieves this is still unknown. Decrease of cellular mRNA is observed during ASFV infection, suggesting that inhibition of cellular proteins is due to an active mRNA degradation process. ASFV carries a gene (Ba71V D250R/Malawi g5R) that encodes a decapping protein (ASFV-DP) that has a Nudix hydrolase motif and decapping activity in vitro. Here, we show that ASFV-DP was expressed from early times and accumulated throughout the infection with a subcellular localization typical of the endoplasmic reticulum, colocalizing with the cap structure and interacting with the ribosomal protein L23a. ASFV-DP was capable of interaction with poly(A) RNA in cultured cells, primarily mediated by the N-terminal region of the protein. ASFV-DP also interacted with viral and cellular RNAs in the context of infection, and its overexpression in infected cells resulted in decreased levels of both types of transcripts. This study points to ASFV-DP as a viral decapping enzyme involved in both the degradation of cellular mRNA and the regulation of viral transcripts.IMPORTANCE Virulent ASFV strains cause a highly infectious and lethal disease in domestic pigs for which there is no vaccine. Since 2007, an outbreak in the Caucasus region has spread to Russia, jeopardizing the European pig population and making it essential to deepen knowledge about the virus. Here, we demonstrate that ASFV-DP is a novel RNA-binding protein implicated in the regulation of mRNA metabolism during infection, making it a good target for vaccine development.
Highlights
African swine fever virus (ASFV) infection is characterized by a progressive decrease in cellular protein synthesis with a concomitant increase in viral protein synthesis, though the mechanism by which the virus achieves this is still unknown
Due to the limited size of their genomes, viruses rely on the host translation machinery for efficient synthesis of their proteins [50]
Our previous results demonstrated that ASFV causes a progressive decrease in poly(A) mRNA signal in the cytoplasm of infected cells, which is detectable at the peripheries of viral factories at late times postinfection [26]
Summary
African swine fever virus (ASFV) infection is characterized by a progressive decrease in cellular protein synthesis with a concomitant increase in viral protein synthesis, though the mechanism by which the virus achieves this is still unknown. We demonstrate that ASFV-DP is a novel RNA-binding protein implicated in the regulation of mRNA metabolism during infection, making it a good target for vaccine development. Uses a specific mechanism of decapping related to cap snatching [4], and vaccinia virus (VACV), which possesses two viral decapping enzymes (D9 and D10) [19, 20] These viral enzymes, which have approximately 25% sequence similarity, possess a Nudix motif, a highly conserved 23-amino-acid sequence (GX5EX5[UA]XREX2EEXGU, where X can be any amino acid and U is a hydrophobic residue). Morphogenesis of the virus takes place in specialized areas of the cytoplasm called viral factories, which are located near the nucleus and the microtubule organization center (MTOC) These structures essentially exclude cellular proteins but are surrounded by endoplasmic reticulum (ER) membranes and enclosed in vimentin cages [23]
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