Human cytomegalovirus UL141 inhibits innate defenses by directly targeting the TRAIL death receptors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F13%3A%230000408" target="_blank" >RIV/00209805:_____/13:#0000408 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.sciencedirect.com/science/article/pii/S1931312813000693" target="_blank" >http://www.sciencedirect.com/science/article/pii/S1931312813000693</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.chom.2013.02.003" target="_blank" >10.1016/j.chom.2013.02.003</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Human cytomegalovirus UL141 inhibits innate defenses by directly targeting the TRAIL death receptors

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Human cytomegalovirus UL141 inhibits innate defenses by directly targeting the TRAIL death receptors

Popis výsledku anglicky

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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

<a href="/cs/project/ED2.1.00%2F03.0101" target="_blank" >ED2.1.00/03.0101: Regionální centrum aplikované molekulární onkologie (RECAMO)</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2013

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Cell Host and Microbe

ISSN

1931-3128

e-ISSN

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Svazek periodika

13

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

324-335

Kód UT WoS článku

000330850400013

EID výsledku v databázi Scopus

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