Gene Discoveries Shed Light on Mpox Virus and Digestive Issues

Medical News: In recent years, the Mpox virus (MPXV) has gained global attention, especially due to its troubling spread and impact. Known for causing fever, headache, and skin rashes, it also leads to gastrointestinal (GI) symptoms such as nausea, diarrhea, and severe abdominal pain. This study explores the virus's effect on the GI system by analyzing gene expression in colon cells, with a focus on identifying genes that MPXV affects, particularly through clades I, IIa, and IIb.


Gene Discoveries Shed Light on Mpox Virus and Digestive Issues
 
Conducted by scientists from the Center for Artificial Intelligence Research at Wake Forest University School of Medicine-USA and George Mason University’s Department of Biology-USA, this research used innovative methods to identify how the virus may affect gene activity in the colon. This Medical News report shares some groundbreaking findings on which genes and biological pathways play a role in the virus's impact on the GI system.
 
Using Advanced Machine Learning to Study the Virus
The research team employed advanced machine learning to analyze RNA sequencing data from human-induced pluripotent stem cell-derived colon cells, or organoids. These organoids model human colon cells, making it easier to detect genetic changes triggered by Mpox (Monkeypox) infection. With machine learning methods, the study identified "differentially expressed genes" (DEGs), which are genes with increased or decreased activity levels in infected cells compared to uninfected cells.
 
This study used RNA data from previous research but implemented new statistical methods to gain deeper insights into MPXV’s impact on the body. The team used a technique called GLMQL-RMAS, which ranks genes based on their biological relevance and statistical significance. Additionally, they employed a machine learning method called Cross-RMAS to categorize and rank genes across three contrasts - mock (uninfected) samples and three different MPXV strains - to better understand how each strain affects the GI system.
 
Findings: Genes and Pathways Impacted by MPXV
The analysis highlighted that MPXV strain I, from the Congo Basin, had the most profound impact on gene expression, particularly upregulating stress-related genes like HSPA6 and FOS, which are important in the body’s response to cellular stress. Other affected genes are linked to protein folding, immune responses, and maintaining epithelial structure, indicating that the virus disrupts essential GI functions.
 
Strain I was found to have a more aggressive effect on gene expression, with over 350 genes showing significant changes, compared to only 82 genes in strain IIa and fewer in strain IIb. The main genes affected across all three strains include HSPA6 and EGR1, which are involved in cellular repair and immune responses, suggesting that stress response mechanisms play a role in the body’s reaction to MPXV.
 
One of the genes affected, HSPA6, is part of a family known as heat shock proteins, whic h help cells manage stress by ensuring proteins are correctly folded. When HSPA6 is overly active, it can trigger immune responses, which can lead to inflammation - a likely factor behind the GI complications associated with the virus.
 
Gene Ontology Analysis Sheds Light on GI Effects
The research team also conducted a gene ontology (GO) analysis, which examines biological processes affected by gene changes. Results showed that MPXV impacts multiple processes, from protein folding and immune responses to nutrient absorption and epithelial structure. The findings suggest that MPXV can disrupt nutrient absorption, immune function, and GI tissue repair, which likely contributes to the abdominal pain, nausea, and diarrhea observed in many patients.
 
In detail, MPXV I affected hundreds of genes associated with GI processes, such as mucosal protection, nutrient absorption, and inflammation regulation. The team identified genes like TFF1 and TFF2, which are essential for maintaining the mucosal barrier that protects the GI lining. This barrier is crucial for preventing infection, which could explain the GI symptoms and inflammation associated with MPXV.
 
New Insights into Strain-Specific Impacts
MPXV I, which showed the most significant gene disruptions, appears to interact with cells more aggressively, impacting cellular structure and immune defenses. By contrast, strains IIa and IIb have a more limited impact, possibly due to different evasion or adaptation strategies. Strain IIb was found to alter fewer genes, including SERPINA3 and GSTA5, which are involved in managing oxidative stress, a type of cellular stress caused by reactive oxygen molecules.
 
Interestingly, the study found that TFF1, a gene linked to epithelial protection and repair, was highly upregulated in response to MPXV infection, specifically by strain I. TFF1 is important in maintaining the integrity of the GI lining, and its upregulation may be part of the body’s response to counteract viral damage. The gene also plays a role in reducing cell death, which is essential in preventing tissue damage in the colon.
 
Using Machine Learning to Differentiate Strains
The team then used a machine learning approach to validate their findings. By training models on the genes impacted by MPXV, they achieved 100% accuracy in identifying different virus strains, highlighting that specific gene changes can help distinguish between them. This approach offers exciting potential for identifying and treating strain-specific symptoms and developing targeted interventions.
 
Using machine learning allowed researchers to identify the unique expression profiles for each MPXV strain. This capability is crucial for distinguishing between strains in a clinical setting, potentially helping doctors determine the best approach to care for patients based on which strain they are infected with.
 
Study Implications and Future Research
This research offers insights into how different MPXV strains affect the GI system, underscoring the importance of specific genes and pathways involved in managing cellular stress and maintaining the GI lining. Future research may focus on further exploring how these findings could guide the development of targeted therapies that alleviate GI symptoms associated with the virus.
 
The study findings were published in the peer-reviewed International Journal of Molecular Sciences.
https://www.mdpi.com/1422-0067/25/20/11142
 
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Read Also:
https://www.thailandmedical.news/news/understanding-the-multi-organ-impact-of-mpox-monkeypox
 
https://www.thailandmedical.news/news/ceo-of-roche-warns-that-lots-of-mpox-cases-in-europe-are-not-being-reported