SARS-CoV-2 Uses Nsp15 Protein to Hide from Immune System and to Replicate Efficiently Which Results in Disease Severity
Nikhil Prasad Fact checked by:Thailand Medical News Team Jun 14, 2025 1 week, 6 days, 1 hour, 51 minutes ago
Thailand Medical News: Scientists Discover How SARS CoV2 Hides from the Immune System Using a Special Protein
A new study has revealed a critical trick that the SARS-CoV-2 virus uses to increase its ability to infect and damage human lungs—it all comes down to a single protein known as nsp15. This protein allows the virus to escape detection by the body’s immune system, helping it replicate more efficiently and cause more severe illness.
SARS-CoV-2 Uses Nsp15 Protein to Hide from Immune System and to Replicate Efficiently Which Results in Disease Severity
Researchers from Boston University’s National Emerging Infectious Diseases Laboratories (NEIDL), Washington University in St. Louis, University of Pittsburgh, and several other U.S. academic institutions collaborated on this groundbreaking research. According to this
Thailand Medical News report, they found that the nsp15 protein has a specific function that allows the virus to silence the body's early warning system, essentially making the infection more stealthy and dangerous.
What Is Nsp15 and Why Is It Important
SARS-CoV-2, the virus behind COVID-19, has a genome that produces 16 nonstructural proteins—these are not part of the virus shell but help it reproduce and avoid being attacked by the immune system. One of these is nsp15, which acts like molecular scissors that cut up a form of viral RNA called double-stranded RNA (dsRNA). This dsRNA is normally what our immune system uses to detect a viral invasion and launch a defense.
By cutting up the dsRNA, nsp15 hides the virus from the immune system. The scientists engineered several mutated versions of SARS-CoV-2 where nsp15 was disabled or altered, and then tested how these mutant viruses behaved in lab-grown human lung cells, mice, and hamsters.
Disabling Nsp15 Makes the Virus Weaker
When the virus could no longer use its nsp15 protein effectively, the results were dramatic. In human stem-cell–derived lung cells, the mutated viruses triggered much stronger immune responses, including the release of antiviral molecules like interferons and interferon-stimulated genes (ISGs). This led to much lower viral replication compared to the normal virus.
In animal tests, mice infected with the nsp15-mutant virus were less likely to die and had reduced viral loads in their lungs and brains. Similarly, hamsters infected with the altered virus showed much lower amounts of virus in their lungs and also displayed stronger immune reactions. These animals recovered better and faster, indicating that nsp15 is a key player in helping the virus cause severe disease.
The Virus Makes Less dsRNA When Nsp15 Is Active
Another key finding was that nsp15 controls the amount of double-stranded RNA inside infected cells. The researchers used imaging techniques to show that cells infected with the mutant virus (lacking nsp15 activity) had significantly higher amounts of dsRNA, which
explains the stronger immune response.
Interestingly, when they treated the infected cells with drugs that block interferon signaling, the mutant virus was able to replicate almost as well as the normal version. This confirms that nsp15’s main job is to help the virus avoid triggering interferon-based immune defenses.
Why This Matters and What Could Be Next
The study has big implications for the future. If researchers can develop drugs that block the action of nsp15, it might allow the body’s natural defenses to detect and fight off SARS-CoV-2 more effectively. It also opens the door to designing weakened forms of the virus that could be used in safe and effective vaccines.
The researchers stress that nsp15 is one of the most important viral tools for hiding from the immune system. By understanding how this protein works, scientists could uncover new ways to treat COVID-19 and even prepare for future coronavirus outbreaks.
In conclusion, the study proves that the endoribonuclease activity of nsp15 is not just a side feature—it is a powerful virulence factor. Without it, the virus is far less dangerous. These insights highlight how SARS-CoV-2 has evolved very specific strategies to avoid immune detection, making it such a formidable virus. Targeting such viral functions may be a game-changer in controlling not only COVID-19 but also other viral diseases that use similar strategies.
The study findings were published in the peer reviewed journal: Proceedings of the National Academy of Sciences (PNAS)
https://www.pnas.org/doi/10.1073/pnas.2426528122
For the latest COVID-19 News, keep on logging to
Thailand Medical News.
Read Also:
https://www.thailandmedical.news/news/researchers-discover-mutation-in-sars-cov-2-nsp15-protein-that-enhances-its-ability-to-evade-immunity
https://www.thailandmedical.news/news/study-finds-that-sars-cov-2-nsp15-suppresses-type-i-interferon-production-by-inhibiting-irf3-phosphorylation-and-nuclear-translocation
https://www.thailandmedical.news/news/covid-19-research-chinese-study-finds-that-sars-cov-2-nsp15-protein-suppresses-type-1-interferon-production
https://www.thailandmedical.news/articles/coronavirus
Share
Tweet
Share
