ERVK Polyprotein Processing and Reverse Transcriptase Expression in Human Cell Line Models of Neurological Disease
Enhanced expression of the reverse transcriptase (RT) protein encoded by human endogenous retrovirus-K (ERVK) is a promising biomarker for several inflammatory and neurological diseases. However, unlike RT enzymes encoded by exogenous retroviruses, little work has been done to identify ERVK RT isofo...
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-01-01
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| Series: | Viruses |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1999-4915/7/1/320 |
| _version_ | 1818979725828161536 |
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| author | Mamneet Manghera Jennifer Ferguson Renée Douville |
| author_facet | Mamneet Manghera Jennifer Ferguson Renée Douville |
| author_sort | Mamneet Manghera |
| collection | DOAJ |
| description | Enhanced expression of the reverse transcriptase (RT) protein encoded by human endogenous retrovirus-K (ERVK) is a promising biomarker for several inflammatory and neurological diseases. However, unlike RT enzymes encoded by exogenous retroviruses, little work has been done to identify ERVK RT isoforms, their expression patterns, and cellular localization. Using Western blot, we showcase the ERVK gag-pro-pol polyprotein processing leading to the production of several ERVK RT isoforms in human neuronal (ReNcell CX) and astrocytic (SVGA) models of neuroinflammatory disease. Since the pro-inflammatory cytokine IFNγ plays a key role in the pathology of several ERVK-associated neurological diseases, we sought to determine if IFNγ can drive ERVK RT expression. IFNγ signalling markedly enhanced ERVK polyprotein and RT expression in both human astrocytes and neurons. RT isoforms were expressed in a cell-type specific pattern and the RT-RNase H form was significantly increased with IFNγ treatment. Fluorescent imaging revealed distinct cytoplasmic, perinuclear and nuclear ERVK RT staining patterns upon IFNγ stimulation of astrocytes and neurons. These findings indicate that ERVK expression is inducible under inflammatory conditions such as IFNγ exposure—and thus, these newly established in vitro models may be useful in exploring ERVK biology in the context of neuroinflammatory disease. |
| first_indexed | 2024-12-20T17:04:06Z |
| format | Article |
| id | doaj.art-e94c72f66d864151b2728488e0218197 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-20T17:04:06Z |
| publishDate | 2015-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-e94c72f66d864151b2728488e02181972022-12-21T19:32:24ZengMDPI AGViruses1999-49152015-01-017132033210.3390/v7010320v7010320ERVK Polyprotein Processing and Reverse Transcriptase Expression in Human Cell Line Models of Neurological DiseaseMamneet Manghera0Jennifer Ferguson1Renée Douville2Department of Biology, University of Winnipeg, Winnipeg, Manitoba R3B 2E9, CanadaDepartment of Biology, University of Winnipeg, Winnipeg, Manitoba R3B 2E9, CanadaDepartment of Biology, University of Winnipeg, Winnipeg, Manitoba R3B 2E9, CanadaEnhanced expression of the reverse transcriptase (RT) protein encoded by human endogenous retrovirus-K (ERVK) is a promising biomarker for several inflammatory and neurological diseases. However, unlike RT enzymes encoded by exogenous retroviruses, little work has been done to identify ERVK RT isoforms, their expression patterns, and cellular localization. Using Western blot, we showcase the ERVK gag-pro-pol polyprotein processing leading to the production of several ERVK RT isoforms in human neuronal (ReNcell CX) and astrocytic (SVGA) models of neuroinflammatory disease. Since the pro-inflammatory cytokine IFNγ plays a key role in the pathology of several ERVK-associated neurological diseases, we sought to determine if IFNγ can drive ERVK RT expression. IFNγ signalling markedly enhanced ERVK polyprotein and RT expression in both human astrocytes and neurons. RT isoforms were expressed in a cell-type specific pattern and the RT-RNase H form was significantly increased with IFNγ treatment. Fluorescent imaging revealed distinct cytoplasmic, perinuclear and nuclear ERVK RT staining patterns upon IFNγ stimulation of astrocytes and neurons. These findings indicate that ERVK expression is inducible under inflammatory conditions such as IFNγ exposure—and thus, these newly established in vitro models may be useful in exploring ERVK biology in the context of neuroinflammatory disease.http://www.mdpi.com/1999-4915/7/1/320endogenous retrovirusreverse transcriptaseastrocyteneuronneurological diseaseinflammationIFNγ |
| spellingShingle | Mamneet Manghera Jennifer Ferguson Renée Douville ERVK Polyprotein Processing and Reverse Transcriptase Expression in Human Cell Line Models of Neurological Disease Viruses endogenous retrovirus reverse transcriptase astrocyte neuron neurological disease inflammation IFNγ |
| title | ERVK Polyprotein Processing and Reverse Transcriptase Expression in Human Cell Line Models of Neurological Disease |
| title_full | ERVK Polyprotein Processing and Reverse Transcriptase Expression in Human Cell Line Models of Neurological Disease |
| title_fullStr | ERVK Polyprotein Processing and Reverse Transcriptase Expression in Human Cell Line Models of Neurological Disease |
| title_full_unstemmed | ERVK Polyprotein Processing and Reverse Transcriptase Expression in Human Cell Line Models of Neurological Disease |
| title_short | ERVK Polyprotein Processing and Reverse Transcriptase Expression in Human Cell Line Models of Neurological Disease |
| title_sort | ervk polyprotein processing and reverse transcriptase expression in human cell line models of neurological disease |
| topic | endogenous retrovirus reverse transcriptase astrocyte neuron neurological disease inflammation IFNγ |
| url | http://www.mdpi.com/1999-4915/7/1/320 |
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