Hungarian Researchers Discover That Viruses Hijack Ancient DNA Loops to Control Human Genes and Trigger Disease
Nikhil Prasad Fact checked by:Thailand Medical News Team Jun 05, 2025 1 week, 6 days, 13 hours, 55 minutes ago
Medical News: In a stunning new discovery, Hungarian researchers have uncovered how viruses manipulate ancient cellular structures known as R-loops to hijack human genetic processes, evade the immune system, and potentially trigger chronic diseases including cancer and autoimmune disorders.
Hungarian Researchers Discover That Viruses Hijack Ancient DNA Loops to Control Human
Genes and Trigger Disease
The groundbreaking research was conducted by scientists from the MTA-DE Momentum Genome Architecture and Recombination Research Group and various departments within the Faculty of Medicine and Pharmacy at the University of Debrecen, Hungary. Their findings shine a spotlight on the quiet yet powerful tug-of-war between invading viruses and the human genome, mediated through R-loops—molecular structures most people have never heard of, but which may hold the key to understanding viral infections and developing new treatments.
R-loops are special three-stranded formations in our DNA where an RNA strand binds back to its original DNA sequence, pushing the other DNA strand aside. While once thought to be rare accidents in the genetic code, scientists now know that R-loops are crucial for controlling which genes are turned on or off. This
Medical News report explores how viruses exploit these structures to gain control inside our bodies.
The Hidden Power of R-loops
R-loops form naturally during the process of gene transcription—when our cells copy DNA into RNA. Normally, they help regulate transcription, ensure correct gene expression, and even repair DNA. However, when not properly managed, these structures can cause chaos by damaging DNA or interfering with replication, potentially leading to serious illnesses like neurodegenerative diseases or cancer.
The study explains that many viruses, including HIV, HPV, hepatitis B, Epstein-Barr, and even SARS-CoV-2, have evolved to exploit R-loops for their benefit. They use these structures to integrate into our genome, remain hidden in our cells for years, and evade immune defenses. In some cases, they even trigger the creation of viral-human hybrid DNA, which can disrupt nearby genes and drive tumor formation.
How Viruses Exploit These Loops
The researchers describe how different classes of viruses—including retroviruses like HIV and DNA viruses like herpesviruses—create or stabilize R-loops during infection. For instance, in the case of Epstein-Barr virus (EBV), R-loops form at the lytic origin of replication, helping the virus multiply. If these R-loops are destroyed, the virus can’t replicate efficiently.
Other viruses manipulate host proteins responsible for resolving R-loops. Influenza A, for example, suppresses immune gene activation by hijacking a host enzyme called SETX, which normally clears R-loops to maintain genetic stability. When SETX is redirected, immune responses are weakened, and the virus can thrive.
HPV (human papillomavirus) provides perhaps the
most chilling example. Its viral proteins degrade p53, a key tumor-suppressor protein, leading to widespread R-loop accumulation at immune genes. This not only silences the body’s defenses but also promotes cancer development by destabilizing the genome.
The Link to Chronic Disease and Autoimmunity
One of the study’s most significant findings is the possible connection between virus-induced R-loop dysregulation and long-term illnesses. When R-loops are left unresolved—either because viruses interfere with the body’s repair machinery or deliberately induce their formation—they can provoke immune responses, DNA damage, or epigenetic changes (altering how genes are expressed without changing the DNA sequence).
Some viruses even produce proteins that mimic human molecules, tricking the immune system or co-opting our regulatory networks. This can cause the immune system to attack healthy tissues, leading to autoimmune diseases. The researchers suggest that SARS-CoV-2’s NSP14 protein might be one such viral mimic, potentially influencing R-loop-related processes to support viral replication or escape detection.
Implications for Future Treatments
The insights from this study point to a new frontier in antiviral therapy: targeting R-loops. If scientists can find ways to stabilize beneficial R-loops or dissolve harmful ones, they may be able to shut down viral replication, awaken dormant viruses for immune clearance, or reduce the risk of virus-related cancers.
Some potential approaches include using drugs that activate enzymes like RNase H or helicases, which naturally clear R-loops. Advanced techniques like CRISPR may one day allow for pinpoint targeting of viral R-loops without harming the host genome.
Additionally, genome-wide mapping technologies such as DRIP-seq (DNA–RNA immunoprecipitation sequencing) could help researchers identify viral R-loop hotspots. This could open the door to precision therapies that specifically target virus-affected areas in the genome.
A New Perspective on Viral Evolution
The study also raises intriguing questions about the long-term relationship between viruses and human evolution. Many ancient viral sequences have become part of our DNA over time. These sequences—called human endogenous retroviruses (HERVs)—still influence gene regulation today, especially in the brain, placenta, and immune system.
R-loops formed in these areas could act as epigenetic regulators, helping turn genes on or off. However, when mismanaged, they might cause genome instability, especially if viruses reactivate or manipulate these sequences. This highlights the dual nature of R-loops—as both guardians and threats to genome health.
Conclusion
The researchers conclude that R-loops are not just accidental byproducts of gene transcription, but are powerful regulatory hubs that viruses have learned to exploit. Viruses manipulate R-loop formation and resolution to gain access to the host genome, suppress immune responses, and ensure their own survival. At the same time, the body uses R-loops as part of its defenses—both to silence invaders and to coordinate responses.
This delicate balancing act between R-loops, host repair systems, and viral strategies reveals a complex evolutionary arms race happening inside every infected cell. As our understanding of R-loops deepens, so does the potential to develop groundbreaking therapies that disrupt these viral tricks and restore the body’s control over its own genome.
The study findings were published in the peer reviewed journal: FEBS Letters.
https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.70086
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