Study Reveals That COVID-19 Alters Key Human Genes

Medical News: COVID-19 and Our Genes: How the Virus Affects Us at the Molecular Level
Researchers from multiple institutions, including the University of Warmia and Mazury in Olsztyn, Poland, have released a study that dives deep into how COVID-19 affects our genes. The study sheds light on how SARS-CoV-2, the virus behind COVID-19, disrupts important gene networks within our bodies. By understanding these disruptions, scientists hope to pave the way for new treatments and ways to predict which patients may experience severe illness.


Graphical Abstract - COVID-19 Alters Key Human Genes
 
This Medical News report explores the study's key findings, focusing on how the virus affects specific genes and pathways that play crucial roles in our immune response and overall health. Through their investigation, the researchers uncovered which genes are altered and how these changes could potentially help or hinder our body’s fight against COVID-19.
 
How SARS-CoV-2 Alters Our Genes
The study involved a meticulous analysis of blood samples from healthy individuals and COVID-19 patients. By sequencing RNA - the genetic material that carries instructions from DNA for producing proteins - the researchers could identify and examine several important changes in gene behavior caused by the virus.
 
Notably, they found that many genes encoding ribosomal proteins, essential for producing other proteins in the cell, were affected. This disruption influenced several key pathways, including those involved in the immune response and viral infection response. Additionally, the virus triggered changes in the way certain genes are expressed, potentially shifting our immune system's ability to fight back.
 
Genetic Variants and Immune Responses
In COVID-19 patients, some genes showed what's called allele-specific expression (ASE). This phenomenon, where different versions of a gene are expressed differently in COVID-19 patients compared to healthy individuals, may indicate why some people react more severely to the virus. These ASE variations were found in genes linked to inflammation, stress response, and immune activation.
 
The research team also observed that certain genes related to immune functions, such as interferon responses, were overactive. For example, the interferon-inducible protein IFI27 showed significantly higher expression in COVID-19 patients, which may help predict the severity of an infection. This finding points to potential biomarkers that could one day help doctors identify patients at high risk of severe illness early on.
 
Alternative Gene Splicing: A New Angle on Viral Impact
Alternative splicing, a process that allows a single gene to produce multiple proteins, was another focus of this research. The virus seemed to influence the splicing of genes involved in immune responses and cellular defense. For example, the OAS1 gene, known to restrict viral infections, displayed altered splicing in COVID-19 patients, potentially impacting its ability to function effect ively against the virus. This alteration may compromise the body's initial defenses, giving the virus a stronger foothold.
 
Circular RNA and Immune Regulation
One fascinating aspect of the study was its examination of circular RNA, a unique form of RNA that forms a closed loop and is highly stable. The virus influenced these circular RNAs, many of which were found to interact with long non-coding RNAs, another type of genetic material that plays a role in regulating genes. These RNA interactions were linked to stress responses and programmed cell death, both of which are essential in managing infections.
 
The virus appeared to silence many of these circular RNAs, possibly undermining a crucial line of defense in our cells. This manipulation may allow SARS-CoV-2 to avoid detection by the immune system, facilitating its spread within the body.
 
Ribosomal Proteins and Cellular Machinery
Among the most impacted genes were those coding for ribosomal proteins, vital components of the cellular machinery that produce proteins. The researchers discovered that COVID-19 patients showed significant disruptions in these genes, which may hinder the body's ability to produce proteins needed for immune responses and recovery. These ribosomal disruptions were linked to pathways such as the coronavirus disease pathway, SARS-CoV-2 host interactions, and immune responses.
 
This discovery suggests that ribosomal proteins play a role beyond simply assembling proteins. In fact, they may act as critical components of our body's response to stress and immune challenges. By disrupting these proteins, SARS-CoV-2 could be stalling the production of new cells needed to replace damaged ones, thus prolonging illness.
 
Examples of Key Human Host Genes that are affected by SARS-CoV-2
Some of the key genes affected by SARS-CoV-2 infection based on the study include:
 
-Interferon Alpha Inducible Protein 27 (IFI27) - Linked with immune response and considered an early predictor of COVID-19 outcomes.
 
-Alpha Kinase 1 (ALPK1) - Associated with inflammatory cytokine and chemokine production.
 
-Mitogen-Activated Protein Kinase 14 (MAPK14) - Plays a crucial role in inflammatory lung injury and cytokine storm, potential therapeutic target.
 
-Caspase Genes (CASP1, CASP4, CASP5) - Involved in inflammation, with CASP1 known to mediate exaggerated inflammatory responses.
 
-Adrenomedullin (ADM) - Related to endothelial integrity, elevated in severe cases of COVID-19.
 
-Ribosomal Protein Genes (RPL and RPS families) - Includes RPL3, RPL7, RPL23A, RPL34, RPS3A, RPS8, RPS15, RPS24, and RPS23. These genes are essential for protein synthesis and have roles in immune response and cell cycle regulation.
 
-Eukaryotic Translation Elongation Factor 1 Alpha 1 (EEF1A1) - Important in protein synthesis, targeted by SARS-CoV-2 to inhibit host protein production.
 
-Makorin Ring Finger Protein 1 (MKRN1) - Has anti-viral functions by interacting with viral RNA and aiding its degradation.
-Eukaryotic Translation Initiation Factor 2 Alpha Kinase 2 (EIF2AK2) - Known for its antiviral properties by inhibiting host and viral mRNA translation.
 
-2'-5'-Oligoadenylate Synthetase 1 (OAS1) - Inhibits viral infections, with variations that affect its antiviral activity.
 
-ADAR (Adenosine Deaminase Acting on RNA) - RNA-editing enzyme with increased expression in severe COVID-19 cases, involved in inflammation.
 
-BAZ1A (Bromodomain Adjacent to Zinc Finger Domain 1A) - Controls chromatin remodeling, potentially involved in gene regulation during infection.
 
-ARL4A (ADP Ribosylation Factor-Like GTPase 4A) - Identified as a biomarker and potential drug target in COVID-19 disease progression.
 
These genes are involved in various critical processes, such as immune signaling, protein synthesis, RNA editing, inflammation, and cellular stress response, all of which are impacted by SARS-CoV-2 infection.
 
Potential for Therapeutic Targets and Early Detection
By identifying specific genes and pathways affected by SARS-CoV-2, this study points toward new avenues for treatment. For instance, targeting genes involved in immune regulation, such as MAPK14, could offer a way to control the excessive inflammatory response, often referred to as the "cytokine storm," which is responsible for severe COVID-19 complications. MAPK14 is one of the core genes linked to acute lung injury, and researchers suggest it could be a promising drug target.
 
Additionally, certain genes affected by COVID-19, such as ADM (Adrenomedullin), may serve as markers for assessing the risk of severe disease progression. ADM, which plays a role in maintaining blood vessel integrity, was significantly elevated in patients experiencing severe COVID-19. Monitoring levels of this gene could help predict complications, including respiratory and cardiovascular issues.
 
Conclusion: Unlocking the Mystery of COVID-19's Impact on Our Genes
In summary, this study provides valuable insights into how SARS-CoV-2 disrupts our genes at multiple levels. By examining changes in gene expression, alternative splicing, allele-specific expression, and circular RNA interactions, the researchers have mapped a complex picture of the virus’s impact on our bodies. These findings lay a foundation for future research, especially in developing targeted therapies and biomarkers that could help doctors better predict and manage severe COVID-19 cases.
 
The study findings were published in the peer-reviewed journal: Computers in Biology and Medicine.
https://www.sciencedirect.com/science/article/pii/S0010482524014288
 
For the latest COVID-19 News, keep on logging to Thailand Medical News.
 
Read Also:
https://www.thailandmedical.news/news/study-reveals-the-sars-cov-2-spike-protein-interacts-with-over-60,000-host-proteins-and-may-trigger-carcinogenesis
 
https://www.thailandmedical.news/news/study-finds-that-sars-cov-2-nsp1-protein-silences-host-genes-involved-in-antiviral-immune-responses