Mpox evades the human immune system by having its viral protein M2 bind to host B7.1 and B7.2 proteins
Nikhil Prasad Fact checked by:Thailand Medical News Team Aug 24, 2024 3 weeks, 4 hours, 55 minutes ago
Medical News: Researchers from Wuhan University and the Wuhan Institute of Virology, Chinese Academy of Sciences in China, have provided new insights into how the Monkeypox virus (MPXV) manages to evade the human immune system. This
Medical News report delves into the intricate mechanisms employed by the MPXV protein M2, which has been found to interfere with crucial immune system processes. This study sheds light on the virus's ability to modulate the immune response, potentially paving the way for new therapeutic approaches.
Mpox evades the human immune system by having its viral protein M2 bind to
host B7.1 and B7.2 proteins
Understanding the Monkeypox Virus and Its Global Impact
Since its identification in 1958, the Monkeypox virus has been a subject of concern due to its sporadic outbreaks, primarily in West and Central Africa. The virus is part of the Orthopoxviridae family, which includes other notable viruses like smallpox. Monkeypox is known for causing skin lesions, fever, headaches, and in some cases, severe complications like encephalitis and septicemia. The global spread of the virus, with over 84,000 cases reported in more than 100 countries as of January 2023, has raised alarms in the global health community. Currently in 2024, there are over 21,000 cases and almost 600 deaths in the African continent caused by a new more lethal and fast spreading strain of the Mpox virus called clade 1b.
The Role of B7 Proteins in Immune Response
The human immune system relies on a complex interplay of molecules to recognize and combat pathogens. Among these, the B7 family proteins, particularly B7.1 (CD80) and B7.2 (CD86), play a pivotal role in activating T cells, which are essential for an effective immune response. These proteins interact with receptors like CD28 and CTLA4 on T cells, facilitating their activation and ensuring the body can mount a defense against infections.
However, the Monkeypox virus, like many other pathogens, has evolved mechanisms to subvert this immune response. The M2 protein of MPXV is one such tool in the virus's arsenal, enabling it to evade detection and destruction by the host's immune system.
How M2 Protein Interferes with Immune Activation
The study conducted by the researchers revealed that the M2 protein of MPXV can bind to the B7.1 and B7.2 proteins on the surface of immune cells. This binding effectively blocks the interaction of these B7 proteins with the CD28 and CTLA4 receptors on T cells. The interruption of this interaction is crucial because it prevents the proper activation of T cells, thereby weakening the immune response.
The researchers used advanced cryo-electron microscopy (cryo-EM) to visualize the structures of the M2 protein in complex with B7.1 and B7.2. They discovered that M2 exists in two forms - hexameric and heptameric - and both forms can bind to B7 proteins with high affinity. This binding creates a physical barrier that prevents the B7 proteins from interacting
with CD28 and CTLA4, effectively subverting the immune response.
Structural Insights into M2 Protein's Function
The cryo-EM analysis provided detailed structural insights into how M2 interacts with B7 proteins. The M2 protein forms an oligomeric ring structure, with B7 proteins binding to the outer face of the M2 ring. The researchers found that the M2 protein binds to the same surface of the B7 proteins that would normally interact with CD28 and CTLA4, effectively outcompeting these receptors and blocking T cell activation.
Interestingly, the binding of M2 to B7 proteins was found to be significantly stronger than the binding of CD28 or CTLA4 to the same proteins. This finding suggests that M2 is highly effective at interfering with T cell activation, which could explain the immune evasion strategies employed by MPXV.
Implications for Immune Evasion and Viral Persistence
The ability of MPXV to evade the immune system through the action of the M2 protein has significant implications for understanding viral persistence and immune evasion. By blocking the activation of T cells, MPXV can effectively escape detection and clearance by the immune system, allowing it to persist in the host for extended periods.
This immune evasion strategy is not unique to MPXV. Other orthopoxviruses, including the vaccinia virus and cowpox virus, also encode M2 proteins with similar functions. The conservation of this mechanism across different orthopoxviruses suggests that it is a critical factor in their ability to cause disease.
Future Directions and Potential Therapeutic Applications
The findings from this study open up new avenues for research into therapeutic interventions that could target the M2 protein and restore proper immune function. By developing drugs or vaccines that can block the interaction between M2 and B7 proteins, it may be possible to enhance the immune response against MPXV and other related viruses.
Furthermore, understanding the structural basis of M2's interaction with B7 proteins could lead to the design of small molecules or antibodies that specifically disrupt this interaction, potentially offering a new class of antiviral therapies.
Conclusion
The study findings highlight the sophisticated strategies employed by the Monkeypox virus to evade the human immune system. The discovery of how the M2 protein interferes with T cell activation provides valuable insights into the virus's ability to persist and cause disease. As researchers continue to unravel the complexities of viral immune evasion, these findings could pave the way for novel therapeutic approaches to combat not only Monkeypox but other related viral infections.
The study findings were published in the peer-reviewed journal Nature Communications.
https://www.nature.com/articles/s41467-023-40748-2
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