About: A Yeast Suppressor Screen Used To Identify Mammalian SIRT1 as a Proviral Factor for Middle East Respiratory Syndrome Coronavirus Replication

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About: A Yeast Suppressor Screen Used To Identify Mammalian SIRT1 as a Proviral Factor for Middle East Respiratory Syndrome Coronavirus Replication Goto Sponge NotDistinct Permalink

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	A Yeast Suppressor Screen Used To Identify Mammalian SIRT1 as a Proviral Factor for Middle East Respiratory Syndrome Coronavirus Replication
Creator	Frieman, Matthew Matthews, Krystal Weston, Stuart Haupt, Rob Kingsbury, Tami Lent, Rachel Vlk, Alexandra
source	Medline; PMC
abstract	Viral proteins must intimately interact with the host cell machinery during virus replication. Here, we used the yeast Saccharomyces cerevisiae as a system to identify novel functional interactions between viral proteins and eukaryotic cells. Our work demonstrates that when the Middle East respiratory syndrome coronavirus (MERS-CoV) ORF4a accessory gene is expressed in yeast it causes a slow-growth phenotype. ORF4a has been characterized as an interferon antagonist in mammalian cells, and yet yeast lack an interferon system, suggesting further interactions between ORF4a and eukaryotic cells. Using the slow-growth phenotype as a reporter of ORF4a function, we utilized the yeast knockout library collection to perform a suppressor screen where we identified the YDL042C/SIR2 yeast gene as a suppressor of ORF4a function. The mammalian homologue of SIR2 is SIRT1, an NAD-dependent histone deacetylase. We found that when SIRT1 was inhibited by either chemical or genetic manipulation, there was reduced MERS-CoV replication, suggesting that SIRT1 is a proviral factor for MERS-CoV. Moreover, ORF4a inhibited SIRT1-mediated modulation of NF-κB signaling, demonstrating a functional link between ORF4a and SIRT1 in mammalian cells. Overall, the data presented here demonstrate the utility of yeast studies for identifying genetic interactions between viral proteins and eukaryotic cells. We also demonstrate for the first time that SIRT1 is a proviral factor for MERS-CoV replication and that ORF4a has a role in modulating its activity in cells. IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) initially emerged in 2012 and has since been responsible for over 2,300 infections, with a case fatality ratio of approximately 35%. We have used the highly characterized model system of Saccharomyces cerevisiae to investigate novel functional interactions between viral proteins and eukaryotic cells that may provide new avenues for antiviral intervention. We identify a functional link between the MERS-CoV ORF4a proteins and the YDL042C/SIR2 yeast gene. The mammalian homologue of SIR2 is SIRT1, an NAD-dependent histone deacetylase. We demonstrate for the first time that SIRT1 is a proviral factor for MERS-CoV replication and that ORF4a has a role in modulating its activity in mammalian cells.
has issue date	2019-05-29(xsd:dateTime)
bibo:doi	10.1128/jvi.00197-19
bibo:pmid	31142674
has license	bronze-oa
sha1sum (hex)	0c5d4c595b4b55bb3a1e0840b78bac81906b365d
schema:url	https://doi.org/10.1128/jvi.00197-19
resource representing a document's title	A Yeast Suppressor Screen Used To Identify Mammalian SIRT1 as a Proviral Factor for Middle East Respiratory Syndrome Coronavirus Replication
has PubMed Central identifier	PMC6675885
has PubMed identifier	31142674
schema:publication	Journal of Virology
resource representing a document's body	covid:0c5d4c595b4b55bb3a1e0840b78bac81906b365d#body_text
is schema:about of	named entity 'The' named entity 'investigate' named entity 'coronavirus' named entity 'gene' named entity 'suppressor' named entity 'functional' named entity 'SIRT1' named entity 'genetic manipulation' named entity 'SIRT1' named entity 'MODULATING' named entity 'MODEL SYSTEM' named entity 'MACHINERY' named entity 'REPLICATION' named entity 'TO IDENTIFY' named entity 'ROLE' named entity 'SIGNALING' named entity 'GENETIC MANIPULATION' named entity 'PERFORM' named entity 'EUKARYOTIC CELLS' named entity 'PRESENTED' named entity 'Viral' named entity 'perform' named entity 'gene' named entity 'ratio' named entity 'proteins' named entity 'homologue' named entity 'time' named entity 'phenotype' named entity 'knockout' named entity 'factor' named entity 'MERS-CoV' named entity 'Saccharomyces cerevisiae' named entity 'viral proteins' named entity 'viral proteins' named entity 'yeast' named entity 'interact' named entity 'functional interactions' named entity 'MERS-CoV' named entity 'case fatality ratio' named entity 'host cell' named entity 'yeast' named entity 'Saccharomyces cerevisiae' named entity 'MERS-CoV' named entity 'SIR2' named entity 'genetic interactions' named entity 'yeast' named entity 'Middle East respiratory syndrome coronavirus' named entity 'mammalian cells' named entity 'mammalian cells' named entity 'mammalian cells' named entity 'proviral' named entity 'virus replication' named entity 'MERS-CoV' named entity 'eukaryotic cells' named entity 'Yeast' named entity 'histone deacetylase' named entity 'infection' named entity 'yeast' named entity 'siRNAs' named entity 'siRNA' named entity 'doxycycline' named entity 'SIRT1' named entity 'infection' named entity 'protein' named entity 'steric' named entity 'luciferase' named entity 'infection' named entity 'cell line' named entity 'bona fide' named entity 'goat' named entity 'Vero' named entity '1:5' named entity 'yeast cells' named entity 'cell lines' named entity 'Huh7'

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