By Jane Cook
28 September 2021
Humans and viruses have been in conflict long before the COVID-19 pandemic. In fact, there is evidence of ancient viral infections embedded in the human genome.
Retroviruses
A class of viruses called retroviruses have left genetic elements behind in the genomes of their vertebrate hosts over the course of millions of years of infections and evolution. It is estimated that 8% or more of the present-day human genome is made up of retroviral genetic elements.
After being incorporated into the genome and passed to the next generation, these retroviral sequences become endogenous, and thus gained the name endogenous retroviruses (ERVs).
Endogenous Retroviruses (ERVs)
Most ERVs are epigenetically silenced by DNA methylation or other silencing mechanisms, although some ERVs are still actively transcribed.
Due to their viral origin, transcribed ERVs are immunogenic, meaning they trigger immune cell responses. Some of the immune activity triggered by ERVs is positive, enhancing the immune system’s ability to respond to certain antigens. However, ERVs have also been linked to the cause of autoimmune disorders and cancers like Hodgkin’s lymphoma, a malignancy of B lymphocyte immune cells.
Anti-tumor Therapies
Researchers studying the complex relationship between ERVs and the immune system discovered that they could manipulate the expression of ERVs using epigenetic drugs and turn them into anti-tumor therapies.
One strategy works for cancers that already have a high level of ERV expression and immune activity, as studied in ovarian tumors. Treating the tumor cells with epigenetic drugs that upregulate ERV expression causes overexpression of the resulting protein and induces cell death.
Awaken the Immune System
The other main strategies involve reactivating silent ERVs to awaken the immune system. This can be done by removing methylation using epigenetic drugs. Reactivating ERVs in cancer cells can cause an immune response to the expressed viral proteins in the tumor cells, thus targeting the immune system to the cancer cells.
This approach is another piece in the puzzle of cancer immunotherapy, an area that holds huge promise for future cancer treatments and is already widely used. To study ERV reactivation, biologists first need to identify which sequence elements in the cancer are retroviral, their methylation state and their RNA expression levels – all jobs for collaborating bioinformaticians.
Jane Cook, Journalist & Content Writer, Bridge Informatics
Jane is a Content Writer at Bridge Informatics, a professional services firm that helps biotech customers implement advanced techniques in management and analysis of genomic data. Bridge Informatics focuses on data mining, machine learning, and various bioinformatic techniques to discover biomarkers and companion diagnostics. If you’re interested in reaching out, please email daniel.dacey@old.bridgeinformatics.com or dan.ryder@old.bridgeinformatics.com.
Sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122352/pdf/cancers-13-01999.pdf
https://www.nature.com/articles/s41586-020-03135-1
https://www.nature.com/articles/s41467-020-17206-4
https://www.nature.com/articles/s42003-021-01800-3
https://www.nature.com/articles/ng.3902
https://www.nature.com/articles/s41579-019-0189-2
https://www.nature.com/articles/s41591-018-0116-5
https://www.nature.com/articles/srep15644
