Study finds that Mpox virus infects human astrocytes, causing neuroinflammation and eventual brain damage!
Nikhil Prasad Fact checked by:Thailand Medical News Team Aug 23, 2024 3 weeks, 8 minutes ago
Mpox News: Unveiling the Link Between Monkeypox Virus and Brain Inflammation: New Insights from a Canadian Study
A recent study led by a team of researchers from the University of Alberta-Canada, University of Texas Southwestern Medical Center, Dallas-USA and the Li Ka Shing Institute of Virology-Canada has shed light on the potential neurotropic and neurovirulent properties of the Monkeypox virus (MPXV). This
Mpox News report delves into how the virus infects human astrocytes, leading to significant brain inflammation and cell death, which could explain the neurological symptoms observed in infected individuals.
MPXV infection of astrocytes and subsequent activation of the inflammasome/pyroptosis cascade. MPVX productively infects human astrocytes causing changes in cell morphology and eventual cell death. MPXV infections activated robust immune responses in human astrocytes including pro-caspase-1 cleavage. Active caspase-1 cleaves GSDMB protein at Lys236 liberating the cytotoxic NT to form pores in the plasma membrane, permitting extravasation of cell contents including mature IL-1β and eventual cell lysis. Of note, while GZMA is known to cleave GSDMB, its presence was not detected in astrocytes. MPXV infection also induces caspase-3 activation that is followed by GFAP degradation and ensuing astrocyte morphological changes.
The Growing Concern of Monkeypox Virus
Monkeypox virus, an orthopoxvirus similar to the more well-known smallpox virus, has been a growing concern since the 2022 outbreak that led the World Health Organization to declare it a global health emergency. While the virus is primarily known for causing skin lesions, fever, and swollen lymph nodes, recent evidence has shown that it also has the potential to cause severe neurological disorders, including headaches, seizures, altered consciousness, and even encephalitis.
In the face of these findings, it has become increasingly important to understand how MPXV affects the brain and what mechanisms are involved in the development of these neurological symptoms. The research has uncovered how MPXV specifically targets astrocytes, the most abundant cell type in the human brain, causing significant cell damage and death through a process known as pyroptosis.
Astrocytes: The Brain's Defenders Turned Victims
Astrocytes play a crucial role in maintaining the health and functionality of the brain. They support neuronal activity, maintain the blood-brain barrier, and are involved in the repair processes following injury. However, when infected by MPXV, these cells become the site of intense viral replication and inflammation.
The study revealed that MPXV preferentially infects astrocytes over other brain cells like neurons and microglia. This selective infection triggers a cascade of inflammatory responses within the astrocytes. The virus activates various immune-related genes, including those responsible for inflammation, which ultimately leads to the rupture of the astrocyte cell membrane - a process known as pyroptosis. This form of cell death is particularly damaging because it not only kills the
infected cell but also releases inflammatory signals into the surrounding tissue, potentially exacerbating brain damage.
Key Study Findings: Understanding the Mechanisms
This article highlights several key findings from the study that deepen our understanding of how MPXV causes brain inflammation and damage:
-Astrocyte Susceptibility: The researchers found that MPXV and its close relative, the Vaccinia virus (VACV), both effectively infect and replicate within astrocytes. However, MPXV was found to be more potent in causing cell death through pyroptosis compared to VACV.
-Inflammatory Response: Upon infection, astrocytes showed increased expression of genes related to inflammation, such as IL12, TNFA, and CASP1. These genes are typically involved in the body's immune response to infection but, in this case, contribute to the damaging inflammatory environment within the brain.
-Gasdermin B Cleavage: A crucial discovery was that MPXV infection leads to the cleavage of Gasdermin B (GSDMB), a protein involved in the pyroptosis process. The cleavage of GSDMB results in the formation of pores in the cell membrane, leading to cell death. This finding is significant because it identifies a potential target for therapeutic intervention.
-Dimethyl Fumarate (DMF) Intervention: The study explored the use of Dimethyl Fumarate (DMF), a drug currently used to treat multiple sclerosis, to inhibit the cleavage of GSDMB. The results were promising, showing that DMF treatment reduced cell death in MPXV-infected astrocytes, suggesting that it could potentially be repurposed as a treatment for MPXV-related neurological complications.
Implications for Future Research and Treatment
The findings of this study are particularly significant in the context of the current MPXV outbreak, as they provide a clearer picture of how the virus can cause severe neurological symptoms. By understanding the mechanisms involved, researchers can begin to develop targeted therapies that could mitigate these effects.
The potential use of DMF as a treatment for MPXV-related brain inflammation is an exciting development. However, further research is needed to confirm its efficacy in vivo and to determine the appropriate dosages and treatment protocols. Additionally, the study's findings open up new avenues for exploring other therapeutic options that could inhibit the pyroptosis pathway, thereby reducing brain damage in infected individuals.
Conclusion
This groundbreaking research highlights the importance of understanding the neurovirulent properties of the Monkeypox virus and its impact on brain health.
As the virus continues to spread and cause concern worldwide, studies like this one provide crucial insights that could lead to the development of effective treatments and preventive measures.
The study findings were published in the peer-reviewed journal: PNAS.
https://www.pnas.org/doi/epub/10.1073/pnas.2315653121
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