About: A genome-wide haploid genetic screen for essential factors in vaccinia virus infection identifies TMED10 as regulator of macropinocytosis

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About: A genome-wide haploid genetic screen for essential factors in vaccinia virus infection identifies TMED10 as regulator of macropinocytosis Goto Sponge NotDistinct Permalink

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	A genome-wide haploid genetic screen for essential factors in vaccinia virus infection identifies TMED10 as regulator of macropinocytosis
Creator	Drexler, Ingo Wiertz, Emmanuel Brummelkamp, Thijn Lebbink, Robert Blomen, Vincent Boer, Ingrid Luteijn, Rutger Sadasivam, Manikam Van Diemen, Ferdy Van Kuppevelt, Toin
source	BioRxiv
abstract	Vaccinia virus is a promising viral vaccine and gene delivery candidate, and has historically been used as a model to study poxvirus-host cell interactions. We employed a genome-wide insertional mutagenesis approach in human haploid cells to identify host factors crucial for vaccinia virus infection. A library of mutagenized HAP1 cells was exposed to Modified Vaccinia Virus Ankara (MVA). Deep-sequencing analysis of virus-resistant cells identified host factors involved in heparan sulfate synthesis, Golgi organization, and vesicular protein trafficking. We validated EXT1, TM9SF2 and TMED10 (TMP21/p23/p24δ) as important host factors for vaccinia virus infection. The critical role of EXT1 in heparan sulfate synthesis and vaccinia virus infection was confirmed. TM9SF2 was validated as a player mediating heparan sulfate expression, explaining its contribution to vaccinia virus infection. In addition, TMED10 was found to be crucial for virus-induced plasma membrane blebbing and phosphatidylserine-induced macropinocytosis, suggesting that TMED10 regulates actin cytoskeleton remodelling necessary for virus infection. Importance Poxviruses are large DNA viruses that can infect a wide range of host species. A number of these viruses are clinically important to humans, including variola virus (smallpox) and vaccinia virus. Since the eradication of smallpox, zoonotic infections with monkeypox virus and cowpox virus are emerging. Additionally, poxviruses can be engineered to specifically target cancer cells, and are used as vaccine vector against tuberculosis, influenza, and coronaviruses. Poxviruses rely on host factors for most stages of their life cycle, including attachment to the cell and entry. These host factors are crucial for virus infectivity and host cell tropism. We used a genome-wide knock-out library of host cells to identify host factors necessary for vaccinia virus infection. We confirm a dominant role for heparin sulfate in mediating virus attachment. Additionally, we show that TMED10, previously not implicated in virus infections, modulates the host cell membrane to facilitate virus uptake.
has issue date	2018-12-11(xsd:dateTime)
bibo:doi	10.1101/493205
has license	biorxiv
sha1sum (hex)	6fba26a85cc21b600807d523b4f94b646918e21b
schema:url	https://doi.org/10.1101/493205
resource representing a document's title	A genome-wide haploid genetic screen for essential factors in vaccinia virus infection identifies TMED10 as regulator of macropinocytosis
schema:publication	bioRxiv
resource representing a document's body	covid:6fba26a85cc21b600807d523b4f94b646918e21b#body_text
is schema:about of	named entity 'genome-wide' named entity 'host factors' named entity 'vaccinia virus' named entity 'infection' named entity 'virus' named entity 'genome-wide' named entity 'heparin sulfate' named entity 'phosphatidylserine' named entity 'life cycle' named entity 'vaccinia virus' named entity 'TMED10' named entity 'Macropinocytosis' named entity 'genome-wide' named entity 'transduced' named entity 'adeno-associated virus' named entity 'amyloid beta peptides' named entity 'TMED10' named entity 'Vaccinia' named entity 'COPI' named entity 'host cell' named entity 'viral vaccine' named entity 'COPI' named entity 'host cell' named entity 'mutagenized' named entity 'trans' named entity 'vaccinia virus' named entity 'endosomal membrane' named entity 'crispr' named entity 'haploid' named entity 'plasma membrane' named entity 'TMED10' named entity 'phalloidin' named entity '7.5' named entity 'prenyltransferase' named entity 'blebbing' named entity 'TMED10' named entity 'actin' named entity 'TMED10' named entity 'transduced' named entity 'presenilin' named entity 'actin' named entity 'actin cytoskeleton' named entity 'TMED10' named entity 'TMED10' named entity 'vaccinia' named entity 'staining' named entity 'Rho GTPase' named entity 'target sequences' named entity 'Vaccinia virus' named entity 'macropinocytosis' named entity 'Golgi' named entity 'cytosolic' named entity 'virus' named entity 'Lassa virus' named entity 'receptor' named entity 'viruses' named entity 'C1 domain' named entity 'sulfation' named entity 'tracrRNA' named entity 'NDST1' named entity 'crRNA' named entity 'genome-wide' named entity 'protein' named entity 'motif' named entity 'macropinocytosis' named entity 'haploid' named entity 'plasma' named entity 'Rac1' named entity 'Rac1' named entity 'virus' named entity 'cellular processes' named entity 'EXT1' named entity 'gRNAs' named entity 'CRISPR' named entity 'RNA'

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