Characterization of Human Herpesvirus 8 genomic integration and amplification events in a primary effusion lymphoma cell line
In this study, we investigated the integration of Human Herpesvirus 8 (HHV-8) into the human genome using the primary effusion lymphoma (PEL) cell line BC-3. Through next-generation sequencing (NGS) data from multiple independent sequencing runs, we identified two highly supported HHV-8 integrants....
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Virology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fviro.2023.1253416/full |
| _version_ | 1797644323970351104 |
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| author | Eva G. Álvarez Eva G. Álvarez Eva G. Álvarez Paula Otero Paula Otero Paula Otero Bernardo Rodríguez-Martín Ana Pequeño-Valtierra Ana Pequeño-Valtierra Iago Otero Iago Otero Iago Otero André Vidal-Capón Jorge Rodríguez-Castro Jorge Rodríguez-Castro Juan J. Pasantes Carmen Rivas Jose M.C. Tubío Jose M.C. Tubío Jose M.C. Tubío Daniel García-Souto Daniel García-Souto Daniel García-Souto |
| author_facet | Eva G. Álvarez Eva G. Álvarez Eva G. Álvarez Paula Otero Paula Otero Paula Otero Bernardo Rodríguez-Martín Ana Pequeño-Valtierra Ana Pequeño-Valtierra Iago Otero Iago Otero Iago Otero André Vidal-Capón Jorge Rodríguez-Castro Jorge Rodríguez-Castro Juan J. Pasantes Carmen Rivas Jose M.C. Tubío Jose M.C. Tubío Jose M.C. Tubío Daniel García-Souto Daniel García-Souto Daniel García-Souto |
| author_sort | Eva G. Álvarez |
| collection | DOAJ |
| description | In this study, we investigated the integration of Human Herpesvirus 8 (HHV-8) into the human genome using the primary effusion lymphoma (PEL) cell line BC-3. Through next-generation sequencing (NGS) data from multiple independent sequencing runs, we identified two highly supported HHV-8 integrants. These integrants encompassed a region of human chromosome 12 that was amplified approximately 16-fold between the junctions. Significantly, these events could represent the first known instance of HHV-8 integration into a hybrid human-viral extrachromosomal chimeric circular DNA (eccDNA). The amplified fragment contained partial or complete copies of various human genes, including SELPLG and CORO1C. Analysis of long-read Nanopore data indicated that the CpGs at the SELPLG promoter were mostly unmethylated, suggesting that the additional copies of SELPLG within this eccDNA are likely transcriptionally active. Our findings suggest that viral insertion and eccDNA amplification could be crucial mechanisms in the development of HHV-8-related cancers. In conclusion, our study provides valuable insights into the molecular mechanisms involved in HHV-8-induced oncogenesis and emphasizes the importance of investigating viral integration and eccDNAs in cancer development. Furthermore, we highlight the necessity of employing multiple independent sequencing approaches to validate integration events and avoid false positives derived from library construction artifacts. |
| first_indexed | 2024-03-11T14:28:52Z |
| format | Article |
| id | doaj.art-18f356a4c6ca41a4988fd671a5d6357f |
| institution | Directory Open Access Journal |
| issn | 2673-818X |
| language | English |
| last_indexed | 2024-03-11T14:28:52Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Virology |
| spelling | doaj.art-18f356a4c6ca41a4988fd671a5d6357f2023-10-31T11:43:04ZengFrontiers Media S.A.Frontiers in Virology2673-818X2023-10-01310.3389/fviro.2023.12534161253416Characterization of Human Herpesvirus 8 genomic integration and amplification events in a primary effusion lymphoma cell lineEva G. Álvarez0Eva G. Álvarez1Eva G. Álvarez2Paula Otero3Paula Otero4Paula Otero5Bernardo Rodríguez-Martín6Ana Pequeño-Valtierra7Ana Pequeño-Valtierra8Iago Otero9Iago Otero10Iago Otero11André Vidal-Capón12Jorge Rodríguez-Castro13Jorge Rodríguez-Castro14Juan J. Pasantes15Carmen Rivas16Jose M.C. Tubío17Jose M.C. Tubío18Jose M.C. Tubío19Daniel García-Souto20Daniel García-Souto21Daniel García-Souto22Genomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, SpainDepartment of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, SpainInstituto de Investigaciones Sanitarias de Santiago de Compostela (IDIS), Santiago de Compostela, SpainGenomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, SpainDepartment of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, SpainInstituto de Investigaciones Sanitarias de Santiago de Compostela (IDIS), Santiago de Compostela, SpainGenomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, SpainGenomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, SpainInstituto de Investigaciones Sanitarias de Santiago de Compostela (IDIS), Santiago de Compostela, SpainGenomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, SpainDepartment of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, SpainInstituto de Investigaciones Sanitarias de Santiago de Compostela (IDIS), Santiago de Compostela, SpainDepartment of Biochemistry, Genetics and Immunology, Universidade de Vigo, Vigo, SpainGenomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, SpainInstituto de Investigaciones Sanitarias de Santiago de Compostela (IDIS), Santiago de Compostela, SpainDepartment of Biochemistry, Genetics and Immunology, Universidade de Vigo, Vigo, SpainViruses and cancer, Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, SpainGenomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, SpainDepartment of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, SpainInstituto de Investigaciones Sanitarias de Santiago de Compostela (IDIS), Santiago de Compostela, SpainGenomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, SpainDepartment of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, SpainInstituto de Investigaciones Sanitarias de Santiago de Compostela (IDIS), Santiago de Compostela, SpainIn this study, we investigated the integration of Human Herpesvirus 8 (HHV-8) into the human genome using the primary effusion lymphoma (PEL) cell line BC-3. Through next-generation sequencing (NGS) data from multiple independent sequencing runs, we identified two highly supported HHV-8 integrants. These integrants encompassed a region of human chromosome 12 that was amplified approximately 16-fold between the junctions. Significantly, these events could represent the first known instance of HHV-8 integration into a hybrid human-viral extrachromosomal chimeric circular DNA (eccDNA). The amplified fragment contained partial or complete copies of various human genes, including SELPLG and CORO1C. Analysis of long-read Nanopore data indicated that the CpGs at the SELPLG promoter were mostly unmethylated, suggesting that the additional copies of SELPLG within this eccDNA are likely transcriptionally active. Our findings suggest that viral insertion and eccDNA amplification could be crucial mechanisms in the development of HHV-8-related cancers. In conclusion, our study provides valuable insights into the molecular mechanisms involved in HHV-8-induced oncogenesis and emphasizes the importance of investigating viral integration and eccDNAs in cancer development. Furthermore, we highlight the necessity of employing multiple independent sequencing approaches to validate integration events and avoid false positives derived from library construction artifacts.https://www.frontiersin.org/articles/10.3389/fviro.2023.1253416/fullHHV-8extrachromosomal chimeric circular DNAprimary effusion lymphomalong-read sequencingcancer |
| spellingShingle | Eva G. Álvarez Eva G. Álvarez Eva G. Álvarez Paula Otero Paula Otero Paula Otero Bernardo Rodríguez-Martín Ana Pequeño-Valtierra Ana Pequeño-Valtierra Iago Otero Iago Otero Iago Otero André Vidal-Capón Jorge Rodríguez-Castro Jorge Rodríguez-Castro Juan J. Pasantes Carmen Rivas Jose M.C. Tubío Jose M.C. Tubío Jose M.C. Tubío Daniel García-Souto Daniel García-Souto Daniel García-Souto Characterization of Human Herpesvirus 8 genomic integration and amplification events in a primary effusion lymphoma cell line Frontiers in Virology HHV-8 extrachromosomal chimeric circular DNA primary effusion lymphoma long-read sequencing cancer |
| title | Characterization of Human Herpesvirus 8 genomic integration and amplification events in a primary effusion lymphoma cell line |
| title_full | Characterization of Human Herpesvirus 8 genomic integration and amplification events in a primary effusion lymphoma cell line |
| title_fullStr | Characterization of Human Herpesvirus 8 genomic integration and amplification events in a primary effusion lymphoma cell line |
| title_full_unstemmed | Characterization of Human Herpesvirus 8 genomic integration and amplification events in a primary effusion lymphoma cell line |
| title_short | Characterization of Human Herpesvirus 8 genomic integration and amplification events in a primary effusion lymphoma cell line |
| title_sort | characterization of human herpesvirus 8 genomic integration and amplification events in a primary effusion lymphoma cell line |
| topic | HHV-8 extrachromosomal chimeric circular DNA primary effusion lymphoma long-read sequencing cancer |
| url | https://www.frontiersin.org/articles/10.3389/fviro.2023.1253416/full |
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