Human cytomegalovirus glycoprotein UL141 targets the TRAIL death receptors to thwart host innate antiviral defenses

Smith, Wendell, Tomasec, Peter, Aicheler, Rebecca, Loewendorf, Andrea, Nemcovicova, Ivana, Wang, Edward Chung Yern ORCID: https://orcid.org/0000-0002-2243-4964, Stanton, Richard James ORCID: https://orcid.org/0000-0002-6799-1182, Macauley, Matt, Norris, Paula, Willen, Laure, Ruckova, Eva, Nomoto, Akio, Schneider, Pascal, Hahn, Gabriele, Zajonc, Dirk M., Ware, Carl F., Wilkinson, Gavin William Grahame ORCID: https://orcid.org/0000-0002-5623-0126 and Benedict, Chris A. 2013. Human cytomegalovirus glycoprotein UL141 targets the TRAIL death receptors to thwart host innate antiviral defenses. Cell Host & Microbe 13 (3) , pp. 324-335. 10.1016/j.chom.2013.02.003

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Abstract

Death receptors (DRs) of the TNFR superfamily contribute to antiviral immunity by promoting apoptosis and regulating immune homeostasis during infection, and viral inhibition of DR signaling can alter immune defenses. Here we identify the human cytomegalovirus (HCMV) UL141 glycoprotein as necessary and sufficient to restrict TRAIL DR function. Despite showing no primary sequence homology to TNF family cytokines, UL141 binds the ectodomains of both human TRAIL DRs with affinities comparable to the natural ligand TRAIL. UL141 binding promotes intracellular retention of the DRs, thus protecting virus infected cells from TRAIL and TRAIL-dependent NK cell-mediated killing. The identification of UL141 as a herpesvirus modulator of the TRAIL DRs strongly implicates this pathway as a regulator of host defense to HCMV and highlights UL141 as a pleiotropic inhibitor of NK cell effector function.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QR Microbiology > QR180 Immunology
Publisher:	Elsevier
ISSN:	1931-3128
Last Modified:	24 Oct 2022 10:37
URI:	https://orca.cardiff.ac.uk/id/eprint/45122

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