Hantavirus inhibits TRAIL-mediated killing of infected cells by downregulating Death Receptor 5
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 viruse...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
20 August 2019
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| In: |
Cell reports
Year: 2019, Volume: 28, Issue: 8, Pages: 2124–2139 |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2019.07.066 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1016/j.celrep.2019.07.066 Verlag, Volltext: https://reader.elsevier.com/reader/sd/pii/S2211124719309702 
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| Author Notes: | Caries Sola-Riera, Shawon Gupta, Kimia T. Maleki, Patricia Gonzalez-Rodriguez, Dale Saidi, Christine L. Zimmer, Sindhu Vangeti, Laura Rivino, Yee-Sin Leo, David Chien Lye, Paul A. MacAry, Clas Ahlm, Anna Smed-Sorensen, Bertrand Joseph, Niklas K. Bjorkstrom, Hans-Gustaf Ljunggren, Jonas Klingstrom |
| Summary: | 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. |
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| Item Description: | Gesehen am 10.12.2019 |
| Physical Description: | Online Resource |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2019.07.066 |