Abstract
Human endogenous retroviruses (HERVs) are retroviral sequences integrated into 8% of the human genome resulting from ancient exogenous retroviral infections. Unlike endogenous retroviruses of other mammalian species, HERVs are mostly replication and retro-transposition defective, and their transcription is strictly regulated by epigenetic mechanisms in normal cells. A significant addition to the growing body of research reveals that HERVs' aberrant activation is often associated with offsetting diseases like autoimmunity, neurodegenerative diseases, cancers, and chemoresistance. Adult T-cell leukemia/lymphoma (ATLL) is a very aggressive and chemoresistant leukemia caused by the human T-cell leukemia virus type 1 (HTLV-1). The prognosis of ATLL remains poor despite several new agents being approved in the last few years. In the present study, we compare the expression of HERV genes in CD8-depleted PBMCs from HTLV-1 asymptomatic carriers and patients with acute ATLL. Herein, we show that HERVs are highly upregulated in acute ATLL. Our results further demonstrate that the oncoprotein Fra-2 binds the LTR region and activates the transcription of several HERV families, including HERV-H and HERV-K families. This raises the exciting possibility that upregulated HERV expression could be a key factor in ATLL development and the observed chemoresistance, potentially leading to new therapeutic strategies and significantly impacting the field of oncology and virology.
Overview
- The study investigates the expression of human endogenous retroviruses (HERVs) in CD8-depleted peripheral blood mononuclear cells (PBMCs) from human T-cell leukemia virus type 1 (HTLV-1) asymptomatic carriers and patients with acute adult T-cell leukemia/lymphoma (ATLL).
- The study compares the expression of HERV genes in CD8-depleted PBMCs from HTLV-1 asymptomatic carriers and patients with acute ATLL. The results show that HERVs are highly upregulated in acute ATLL. The study further demonstrates that the oncoprotein Fra-2 binds the LTR region and activates the transcription of several HERV families, including HERV-H and HERV-K families. This raises the possibility that upregulated HERV expression could be a key factor in ATLL development and the observed chemoresistance, potentially leading to new therapeutic strategies and significantly impacting the field of oncology and virology.
Comparative Analysis & Findings
- The study compares the expression of HERV genes in CD8-depleted PBMCs from HTLV-1 asymptomatic carriers and patients with acute ATLL. The results show that HERVs are highly upregulated in acute ATLL. The study further demonstrates that the oncoprotein Fra-2 binds the LTR region and activates the transcription of several HERV families, including HERV-H and HERV-K families. This raises the possibility that upregulated HERV expression could be a key factor in ATLL development and the observed chemoresistance, potentially leading to new therapeutic strategies and significantly impacting the field of oncology and virology.
Implications and Future Directions
- The study's findings suggest that HERVs play a crucial role in the development and chemoresistance of ATLL. Further research is needed to validate these findings and explore the potential of targeting HERVs as a therapeutic strategy for ATLL. Additionally, the study highlights the importance of understanding the epigenetic mechanisms that regulate HERV expression in normal cells and their dysregulation in cancer. Future studies should investigate the role of HERVs in other cancers and explore the potential of targeting HERVs as a therapeutic strategy for these cancers as well.