Reovirus Activated Cell Death Pathways
Mammalian orthoreoviruses (ReoV) are non-enveloped viruses with segmented double-stranded RNA genomes. In humans, ReoV are generally considered non-pathogenic, although members of this family have been proven to cause mild gastroenteritis in young children and may contribute to the development of in...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/11/1757 |
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| author | Carly DeAntoneo Pranav Danthi Siddharth Balachandran |
| author_facet | Carly DeAntoneo Pranav Danthi Siddharth Balachandran |
| author_sort | Carly DeAntoneo |
| collection | DOAJ |
| description | Mammalian orthoreoviruses (ReoV) are non-enveloped viruses with segmented double-stranded RNA genomes. In humans, ReoV are generally considered non-pathogenic, although members of this family have been proven to cause mild gastroenteritis in young children and may contribute to the development of inflammatory conditions, including Celiac disease. Because of its low pathogenic potential and its ability to efficiently infect and kill transformed cells, the ReoV strain Type 3 Dearing (T3D) is clinical trials as an oncolytic agent. ReoV manifests its oncolytic effects in large part by infecting tumor cells and activating programmed cell death pathways (PCDs). It was previously believed that apoptosis was the dominant PCD pathway triggered by ReoV infection. However, new studies suggest that ReoV also activates other PCD pathways, such as autophagy, pyroptosis, and necroptosis. Necroptosis is a caspase-independent form of PCD reliant on receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and its substrate, the pseudokinase mixed-lineage kinase domain-like protein (MLKL). As necroptosis is highly inflammatory, ReoV-induced necroptosis may contribute to the oncolytic potential of this virus, not only by promoting necrotic lysis of the infected cell, but also by inflaming the surrounding tumor microenvironment and provoking beneficial anti-tumor immune responses. In this review, we summarize our current understanding of the ReoV replication cycle, the known and potential mechanisms by which ReoV induces PCD, and discuss the consequences of non-apoptotic cell death—particularly necroptosis—to ReoV pathogenesis and oncolysis. |
| first_indexed | 2024-03-10T01:25:17Z |
| format | Article |
| id | doaj.art-e29dd02cdb1a4fd396a6433808e62820 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T01:25:17Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-e29dd02cdb1a4fd396a6433808e628202023-11-23T13:52:16ZengMDPI AGCells2073-44092022-05-011111175710.3390/cells11111757Reovirus Activated Cell Death PathwaysCarly DeAntoneo0Pranav Danthi1Siddharth Balachandran2Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USADepartment of Biology, Indiana University, Bloomington, IN 47405, USABlood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USAMammalian orthoreoviruses (ReoV) are non-enveloped viruses with segmented double-stranded RNA genomes. In humans, ReoV are generally considered non-pathogenic, although members of this family have been proven to cause mild gastroenteritis in young children and may contribute to the development of inflammatory conditions, including Celiac disease. Because of its low pathogenic potential and its ability to efficiently infect and kill transformed cells, the ReoV strain Type 3 Dearing (T3D) is clinical trials as an oncolytic agent. ReoV manifests its oncolytic effects in large part by infecting tumor cells and activating programmed cell death pathways (PCDs). It was previously believed that apoptosis was the dominant PCD pathway triggered by ReoV infection. However, new studies suggest that ReoV also activates other PCD pathways, such as autophagy, pyroptosis, and necroptosis. Necroptosis is a caspase-independent form of PCD reliant on receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and its substrate, the pseudokinase mixed-lineage kinase domain-like protein (MLKL). As necroptosis is highly inflammatory, ReoV-induced necroptosis may contribute to the oncolytic potential of this virus, not only by promoting necrotic lysis of the infected cell, but also by inflaming the surrounding tumor microenvironment and provoking beneficial anti-tumor immune responses. In this review, we summarize our current understanding of the ReoV replication cycle, the known and potential mechanisms by which ReoV induces PCD, and discuss the consequences of non-apoptotic cell death—particularly necroptosis—to ReoV pathogenesis and oncolysis.https://www.mdpi.com/2073-4409/11/11/1757reovirusnecroptosisapoptosisoncolysisZBP1RIPK3 |
| spellingShingle | Carly DeAntoneo Pranav Danthi Siddharth Balachandran Reovirus Activated Cell Death Pathways Cells reovirus necroptosis apoptosis oncolysis ZBP1 RIPK3 |
| title | Reovirus Activated Cell Death Pathways |
| title_full | Reovirus Activated Cell Death Pathways |
| title_fullStr | Reovirus Activated Cell Death Pathways |
| title_full_unstemmed | Reovirus Activated Cell Death Pathways |
| title_short | Reovirus Activated Cell Death Pathways |
| title_sort | reovirus activated cell death pathways |
| topic | reovirus necroptosis apoptosis oncolysis ZBP1 RIPK3 |
| url | https://www.mdpi.com/2073-4409/11/11/1757 |
| work_keys_str_mv | AT carlydeantoneo reovirusactivatedcelldeathpathways AT pranavdanthi reovirusactivatedcelldeathpathways AT siddharthbalachandran reovirusactivatedcelldeathpathways |