Study Finds That SARS-CoV-2 NSP6 Protein Triggers Cell Cleanup Then Shuts It Down to Evade Immune Attack
Nikhil Prasad Fact checked by:Thailand Medical News Team Apr 15, 2025 22 hours, 49 minutes ago
Medical News:
COVID Protein NSP6 Disrupts Body’s Natural Cellular Cleanup Process While Also Triggering It
A new study by researchers from the College of Life and Health Science at Northeastern University in Shenyang, China, has shed light on a disturbing tactic used by the SARS-CoV-2 virus to exploit human cells. The virus appears to hijack a critical cellular process known as autophagy—a built-in system that cells use to clean up and recycle waste materials—and turns it to its advantage. The key culprit in this manipulation is a viral protein called non-structural protein 6 or NSP6.
Study Finds That SARS-CoV-2 NSP6 Protein Triggers Cell Cleanup Then Shuts It Down to Evade Immune Attack
Autophagy plays an essential role in fighting off viral infections by trapping and destroying unwanted materials, including virus particles, in special compartments called autophagosomes. These are then merged with lysosomes—cellular structures filled with digestive enzymes—to break everything down. However, this
Medical News report reveals that NSP6 from the SARS-CoV-2 virus can both initiate and sabotage this vital cleanup process in the host cells.
A Double-Edged Strategy by the Virus
According to the findings, NSP6 kickstarts the process of autophagy by activating a protein known as Beclin1. This action helps generate autophagosomes—the cellular garbage trucks that collect unwanted debris. At first glance, this would seem like the virus is encouraging its own destruction.
But the twist comes later. Once the autophagosomes are formed, NSP6 throws a wrench into the final phase of the process. It blocks the fusion of autophagosomes with lysosomes by interfering with a key protein called Mucolipin 1 (MLN1). This blockage means the waste, including viral components, is collected but not destroyed. Instead, these waste-filled compartments accumulate inside cells, possibly allowing the virus to hide from the immune system and continue replicating.
A mutation in NSP6, known as L37F, was also investigated in the study. This variant has been linked to milder or asymptomatic cases of COVID-19. Intriguingly, L37F still promotes the early stages of autophagy but is less efficient at stopping the final clean-up step. Researchers observed that this mutant form does not bind as tightly to MLN1, resulting in a more complete autophagy process that may explain why infections with the L37F variant are less severe.
Lab Experiments Reveal Viral Trickery
The research team used various advanced lab techniques to study these effects, including fluorescence microscopy and protein interaction analyses in human cell cultures. They found that cells expressing either the original NSP6 or the L37F variant showed increased levels of LC3-II—a protein marker that indicates autophagy is underway.
However, only cells with the original NSP6 showed high levels of a protein called P62, which typically gets degraded if autoph
agy is working properly. The accumulation of P62 pointed to a blockage in the cellular degradation system, caused by NSP6’s interference with MLN1.
Additional experiments confirmed that NSP6 directly binds to the MLN1 protein and prevents it from functioning. In contrast, L37F had a weaker interaction with MLN1, which allowed some of the waste to be degraded normally. This discovery further supports the idea that the L37F mutation makes the virus less capable of disrupting normal cellular processes, possibly explaining its association with asymptomatic cases.
Why These Findings Matter
The dual nature of NSP6—activating autophagy while simultaneously blocking it—may be one of the reasons why the SARS-CoV-2 virus is so adept at evading immune responses. By initiating the process, the virus might trick the cell into a false sense of security, only to later disrupt the cleanup and allow itself to hide or replicate unchallenged.
Understanding this mechanism opens up exciting possibilities for new COVID-19 treatments. For instance, targeting the interaction between NSP6 and MLN1 or enhancing MLN1 function could restore normal autophagic degradation and help the body eliminate the virus more effectively. Similarly, blocking NSP6’s ability to activate Beclin1 might prevent the virus from misusing the cell’s cleanup machinery in the first place.
Study Conclusion
The study concluded that SARS-CoV-2 NSP6 plays a deceptive and dual role in manipulating host cell autophagy. While it promotes the formation of autophagosomes through Beclin1 activation, it simultaneously hinders the final degradation step by binding to MLN1. This leads to an accumulation of cellular waste and viral proteins that the body cannot clear efficiently. The L37F variant of NSP6, which is associated with less severe infections, shows a reduced ability to interfere with MLN1, offering insights into viral attenuation and potential therapeutic targets. These findings suggest that therapeutics aimed at restoring autophagic degradation could be a powerful strategy in managing COVID-19 and similar viral infections.
The study findings were published in the peer reviewed International Journal of Molecular Sciences.
https://www.mdpi.com/1422-0067/26/8/3699
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Read Also:
https://www.thailandmedical.news/news/cellular-autophagy-in-human-metapneumovirus-hmpv-infections
https://www.thailandmedical.news/news/study-finds-that-sars-cov-2-orf3a-protein-triggers-cell-death-by-damaging-lysosomes
https://www.thailandmedical.news/news/small-protein-pesp-found-to-boost-influenza-virus-replication-by-enhancing-autophagy
https://www.thailandmedical.news/articles/coronavirus
https://www.thailandmedical.news/pages/thailand_doctors_listings
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