Viral Proteases Can Bind to Nucleosomal DNA and Cleave Nuclear cGAS That Attenuates Type I Interferon
Nikhil Prasad Fact checked by:Thailand Medical News Team Feb 27, 2025 4 hours, 48 minutes ago
Medical News: Scientists Discover How a Viral Protein Weakens The Immune System
A team of international researchers has made a significant breakthrough in understanding how certain viruses can weaken the body's immune response. The study, conducted by scientists from China Agricultural University, Harbin Veterinary Research Institute, and Texas A&M University, reveals that a viral protease binds to nucleosomal DNA and cleaves nuclear cGAS, thereby suppressing the body’s ability to fight infections.
Viral Proteases Can Bind to Nucleosomal DNA and Cleave Nuclear cGAS That Attenuates Type I Interferon
This
Medical News report highlights how these findings could have major implications for understanding viral immune evasion strategies and potentially developing new antiviral therapies.
Understanding The Role Of cGAS In Immune Defense
The human body relies on its immune system to detect and combat invading viruses. One key player in this defense is a molecule called cyclic GMP-AMP synthase (cGAS), which recognizes viral DNA and triggers the production of type I interferons - proteins that help the body mount an antiviral response. When viruses find ways to bypass or inhibit this response, they can spread more easily and cause severe diseases.
How The Viral Protease Disrupts Immunity
The study focused on Seneca Valley virus (SVV), a type of picornavirus, and its protease 3C, which is known to enter the nucleus of host cells. Researchers found that SVV 3C protease has a unique ability to bind to nucleosomal DNA, the structure that holds genetic material within the nucleus. This interaction enhances the protease’s ability to cleave cGAS, particularly at its N-terminal domain, leading to the suppression of type I interferon production.
The Key Findings of The Study
-SVV 3C Protease Translocates into The Nucleus: The study revealed that SVV infection induces the translocation of its 3C protease from the cytoplasm into the nucleus. Once inside, it interacts with the host’s nucleosomal DNA.
-Cleavage Of Nuclear cGAS: The protease specifically targets the N-terminal domain of cGAS, which is critical for its immune function. This prevents cGAS from moving to the cytoplasm, thereby stopping the activation of the immune response.
-DNA Binding Enhances Cleavage Activity: Researchers observed that the presence of double-stranded DNA significantly enhances the cleavage activity of the viral protease. This suggests that DNA plays a role in promoting the protease’s ability to disrupt immune signaling.
-Histone H2A Degradation: In addition to cleaving cGAS, SVV 3C also degrades histone H2A, a protein essential for maintaining chromatin integrity. This disruption could further facilitate viral replication and spread within the host.
&
;nbsp;
Implications For Antiviral Research
These findings provide valuable insights into how viruses evade immune detection. By preventing cGAS from activating the interferon response, SVV ensures that it can persist within the host without triggering an effective defense. This mechanism may not be limited to SVV alone, as other viruses could employ similar strategies to suppress immune responses.
Understanding this viral strategy opens new avenues for developing antiviral drugs that target protease activity. Scientists are now exploring ways to design inhibitors that could block the protease from binding to DNA or cleaving cGAS, which could restore the immune system’s ability to detect and eliminate viral infections.
Conclusion
This study sheds light on a novel viral immune evasion mechanism, demonstrating that SVV 3C protease binds to nucleosomal DNA and cleaves nuclear cGAS to suppress type I interferon signaling. The findings highlight the sophisticated strategies employed by viruses to manipulate host defenses. Future research will focus on identifying potential inhibitors of SVV 3C protease, which could serve as a foundation for new antiviral therapies. Given the broad implications of this discovery, further studies are needed to determine whether similar mechanisms exist in other viral families and how they might be countered.
The study findings were published in the peer-reviewed journal: mBio.
https://journals.asm.org/doi/10.1128/mbio.03395-24
For the latest on Viruses and the Human Immune System, keep on logging to Thailand
Medical News.
Read Also:
https://www.thailandmedical.news/news/american-study-finds-that-viral-superinfection-can-trigger-anti-hla-antibodies
https://www.thailandmedical.news/news/virus-induced-pathogenic-antibodies-lessons-from-long-covid-and-dengue
https://www.thailandmedical.news/news/indonesian-study-explores-viruses-and-their-link-to-oral-potentially-malignant-disorders
https://www.thailandmedical.news/news/thailand-doctors-discover-natural-compounds-that-kill-deadly-viruses-including-sars-cov-2-and-flu-viruses
https://www.thailandmedical.news/pages/thailand_doctors_listings
Share
Tweet
Share
