Characterization of Human Herpesvirus 8 genomic integration and amplification events in a primary effusion lymphoma cell line

Frontiers in Virology

Virology

Juan J. Pasantes¹  André Vidal-Capón¹  Bernardo Rodríguez-Martín²  Jose M.C. Tubío³  Iago Otero³  Eva G. Álvarez³  Daniel García-Souto³  Paula Otero³  Jorge Rodríguez-Castro⁴  Ana Pequeño-Valtierra⁴  Carmen Rivas⁵ 

[1] Department of Biochemistry, Genetics and Immunology, Universidade de Vigo, Vigo, Spain;Genomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain;Genomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain;Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, Spain;Instituto de Investigaciones Sanitarias de Santiago de Compostela (IDIS), Santiago de Compostela, Spain;Genomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain;Instituto de Investigaciones Sanitarias de Santiago de Compostela (IDIS), Santiago de Compostela, Spain;Viruses and cancer, Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain;

关键词: HHV-8;    extrachromosomal chimeric circular DNA;    primary effusion lymphoma;    long-read sequencing;    cancer;   

DOI  :  10.3389/fviro.2023.1253416

 received in 2023-07-05, accepted in 2023-09-14,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

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Copyright © 2023 Álvarez, Otero, Rodríguez-Martín, Pequeño-Valtierra, Otero, Vidal-Capón, Rodríguez-Castro, Pasantes, Rivas, Tubío and García-Souto