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Title: Hantavirus Inhibits TRAIL-Mediated Killing of Infected Cells by Downregulating Death Receptor 5
Authors: Solà-Riera, C.
Gupta, S.
Maleki, K.T.
González-Rodriguez, P.
Saidi, D.
Zimmer, C.L.
Vangeti, S.
Rivino, L.
Leo, Y.-S.
Lye, D.C.
MacAry, P.A. 
Ahlm, C.
Smed-Sörensen, A.
Joseph, B.
Björkström, N.K.
Ljunggren, H.-G.
Klingström, J.
Keywords: apoptosis
death receptor 5
dengue virus
RNA virus
Issue Date: 2019
Publisher: Elsevier B.V.
Citation: Solà-Riera, C., Gupta, S., Maleki, K.T., González-Rodriguez, P., Saidi, D., Zimmer, C.L., Vangeti, S., Rivino, L., Leo, Y.-S., Lye, D.C., MacAry, P.A., Ahlm, C., Smed-Sörensen, A., Joseph, B., Björkström, N.K., Ljunggren, H.-G., Klingström, J. (2019). Hantavirus Inhibits TRAIL-Mediated Killing of Infected Cells by Downregulating Death Receptor 5. Cell Reports 28 (8) : 2124-2139000000. ScholarBank@NUS Repository.
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
Abstract: Cytotoxic lymphocytes normally kill virus-infected cells by apoptosis induction. Cytotoxic granule-dependent apoptosis induction engages the intrinsic apoptosis pathway, whereas death receptor (DR)-dependent apoptosis triggers the extrinsic apoptosis pathway. Hantaviruses, single-stranded RNA viruses of the order Bunyavirales, induce strong cytotoxic lymphocyte responses in infected humans. Cytotoxic lymphocytes, however, are largely incapable of eradicating hantavirus-infected cells. Here, we show that the prototypic hantavirus, Hantaan virus (HTNV), induces TRAIL production but strongly inhibits TRAIL-mediated extrinsic apoptosis induction in infected cells by downregulating DR5 cell surface expression. Mechanistic analyses revealed that HTNV triggers both 26S proteasome-dependent degradation of DR5 through direct ubiquitination of DR5 and hampers DR5 transport to the cell surface. These results corroborate earlier findings, demonstrating that hantavirus also inhibits cytotoxic cell granule-dependent apoptosis induction. Together, these findings show that HTNV counteracts intrinsic and extrinsic apoptosis induction pathways, providing a defense mechanism utilized by hantaviruses to inhibit cytotoxic cell-mediated eradication of infected cells. © 2019 The Author(s)Cytotoxic lymphocytes normally kill virus-infected cells by inducing apoptosis. Solà-Riera et al. demonstrate that the RNA virus Hantaan virus efficiently downregulates DR5 cell surface expression by initially triggering a transient 26S proteasome-dependent degradation of DR5 and later hampering DR5 intracellular transport, thus efficiently inhibiting TRAIL-mediated apoptosis of infected cells. © 2019 The Author(s)
Source Title: Cell Reports
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2019.07.066
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
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