Past study shows that Monkeypox (Mpox) virus is able to suppress both CD4 and CD8 T cell activation
Nikhil Prasad Fact checked by:Thailand Medical News Team Sep 04, 2024 2 months, 2 weeks, 6 days, 17 hours, 10 minutes ago
Medical News: A past study conducted by researchers from the Vaccine and Gene Therapy Institute at Oregon Health and Science University-USA, along with the Torrey Pines Institute for Molecular Studies, California-USA had revealed a remarkable discovery about how the monkeypox (Mpox) virus or MPV, evades human immune responses. The study sheds light on how the virus suppresses the body’s natural defense mechanisms, particularly its ability to block antiviral T cell responses. This
Medical News report will explore these findings, which highlight MPV's unique strategy for immune evasion. These insights could be pivotal for developing new therapies or vaccines aimed at combating viral infections.
Past study shows that Monkeypox (Mpox) virus is able to suppress both CD4
and CD8 T cell activation
Understanding the Immune Evasion Tactics
MPV, a virus closely related to smallpox, has long been a concern due to its virulence and potential use as a bioterrorism agent. The 2003 outbreak of MPV in the United States provided a crucial opportunity for scientists to study how the immune system reacts to this virus. A key component of our immune defense is the activation of CD4+ and CD8+ T cells, which are designed to recognize and attack viral infections. However, the study published by Professor Dr Hammarlund and her colleagues reveals that MPV has developed an exceptional ability to avoid detection by these crucial immune cells.
MPV does not follow the typical immune evasion pathways seen in other viruses like cowpox, which interfere with MHC (Major Histocompatibility Complex) expression. Instead, MPV uses a mechanism that suppresses T cell activation without affecting the MHC pathway.
Key Findings: MPV vs. T Cell Responses
Researchers conducted tests on individuals who had been vaccinated against vaccinia virus (VV), a virus used in smallpox vaccines, to assess the cross-reactive immune response against MPV. Surprisingly, while VV-infected cells were easily recognized and targeted by T cells, MPV-infected cells evaded the immune response. The study found that MPV-infected cells were not recognized by the CD4+ and CD8+ T cells, leading to significantly reduced inflammatory cytokine production.
Further tests on blood samples from both vaccinia-immune and MPV-immune individuals showed a consistent pattern: MPV suppressed T cell responses by more than 90%. These results suggested that MPV might be suppressing T cell receptor activation, a mechanism that is unique compared to other poxviruses like cowpox.
A Closer Look at MHC Class I and II Expression
One of the most surprising findings was that MPV does not downregulate MHC class I or II molecules on infected cells, unlike cowpox, which is known to interfere with MHC class I transport. In simpler terms, MPV avoids detection by the immune system without the usual strategy of reducing MHC expression. Instead, MPV-infected cells can effectively prevent the activation of T cells through other yet-to-be-identified factors. This suppression is believed to help the
virus spread in the host without triggering a full-blown immune response.
The Power of Bystander Suppression
An intriguing aspect of the study was the discovery that MPV could suppress T cell responses even when cells were co-infected with vaccinia virus. When cells were exposed to both viruses simultaneously, MPV dominated, reducing T cell activation by nearly 95%. This finding led researchers to hypothesize that MPV might be producing a factor that can block T cell activation not only in infected cells but also in nearby uninfected cells. This trans inhibition suggests that MPV uses a powerful, widespread immune evasion strategy.
Mechanism of MPV Suppression
The research team also investigated whether MPV produced a secreted factor that inhibits immune responses. By isolating infected cells and removing any secreted proteins, they demonstrated that the suppression required direct cell-to-cell contact. The MPV-induced suppression was not caused by any secreted substances, reinforcing the idea that the virus’s evasion mechanism operates within infected cells through an unknown protein or viral product.
Interestingly, when researchers used UV-inactivated MPV, the immune system was able to recognize the virus and activate T cells. This implies that live MPV produces an early gene product that blocks T cell activation and prevents the immune system from responding effectively.
Implications for Future Therapies
The findings of this study are highly significant for the development of future vaccines and antiviral therapies. Understanding how MPV evades the immune system could pave the way for new biologics that target the virus’s suppression mechanisms. Additionally, identifying the viral factors responsible for immune suppression could help in developing treatments that prevent T cell-mediated diseases.
Conclusions
The study by Hammarlund et al. has revealed critical insights into how monkeypox virus suppresses the human immune system. By preventing T cell activation, MPV is able to evade detection and continue spreading within the host. The virus does this without altering MHC expression, suggesting that it uses a novel immune evasion mechanism. These findings open the door to potential new therapies that could target the virus’s suppression mechanisms, offering hope for better protection against MPV and related poxviruses in the future.
The study findings were published in the peer-reviewed journal: Proceedings of the National Academy of Sciences (PNAS).
https://www.pnas.org/doi/full/10.1073/pnas.0800589105
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Read Also:
https://www.thailandmedical.news/news/scientists-warned-in-2009-that-vaccinia-virus-in-current-mpox-vaccines-impairs-critical-immune-functions
https://www.thailandmedical.news/news/italian-study-finds-that-the-immune-system-relies-more-heavily-on-cd4-t-cells-in-the-fight-against-mpox
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