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In a recent study, researchers from the United States, Brazil, and Germany uncovered key insights into how SARS-CoV-2 and its variants evade the immune system. These discoveries pave the way for developing new treatments for COVID-19. The findings were published in the journal Cell on May 9, 2024, under the title “Evasion of NKG2D-mediated cytotoxic immunity by sarbecoviruses.”

The study discovered that cells infected with SARS-CoV-2 reduce the expression of crucial immune signals known as NKG2D ligands. These ligands play a vital role in activating the immune system, particularly natural killer (NK) cells, which are key components of the innate immune response against viral infections.

Moreover, the researchers identified the mechanism by which SARS-CoV-2 downregulates these immune signals. They found that a viral protein called ORF6 is significantly involved in this process. Interestingly, an antibody named 7C6, previously used in cancer research, can block this downregulation and help NK cells better recognize and eliminate infected cells. This discovery paves the way for developing new therapies targeting COVID-19.

Additionally, the study highlighted the importance of NK cells in combating cells infected with SARS-CoV-2. Despite the virus's efforts to suppress the immune system, NK cells can still identify and destroy infected cells. This suggests that activating the innate immune system might be a promising strategy for treating COVID-19.

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Credit: Cell(2024), DOI:10.1016/j.cell.2024.03.026

Dr. Angelique Hölzemer, the head of the Infection and Immune Regulation Research Group at the Leibniz Institute for Virology in Germany, stated, "Our findings provide critical insights into the immune defenses against SARS-CoV-2 and how new therapies can enhance these defenses. By gaining a better understanding of how this virus attempts to evade the immune system, we can develop more methods to treat COVID-19."

References

[1] Jordan A. Hartmann et al. Evasion of NKG2D-mediated cytotoxic immunity by sarbecoviruses. Cell, 2024, doi:10.1016/j.cell.2024.03.026.

[2] Mechanism for immune evasion of SARS-CoV-2 identified
https://www.uke.de/english/departments-institutes/institutes/infection-research-and-vaccine-development/news/index.html