BREAKING! Thousands of Novel Hybrid Genes or Chimeric RNAs Found in the Blood of the COVID-19 Infected!

Medical News: In a groundbreaking study that adds yet another twist to the complex story of COVID-19, scientists have discovered thousands of unusual genetic structures called chimeric RNAs - essentially hybrid gene transcripts - in the blood of people infected with the SARS-CoV-2 virus. These strange molecular entities, also known as hybrid genes, appear to be a previously overlooked feature of the virus's impact on human biology and may help explain some of the varied and persistent symptoms experienced by patients.


BREAKING! Thousands of Novel Hybrid Genes or Chimeric RNAs Found in the Blood of the COVID-19 Infected!

The research was carried out by a team of scientists from multiple institutions, including the University of Virginia School of Medicine-USA (Departments of Biochemistry and Molecular Genetics, and Pathology), the Union Hospital and Tongji Medical College of Huazhong University of Science and Technology in Wuhan, China, the National Clinical Research Center for Gynecology and Obstetrics, Zhengzhou University, and the CSIR-Indian Institute of Toxicology Research in India.
 
This Medical News report delves deep into their findings and the potentially transformative implications of this novel area of discovery.
 
A Massive and Unusual Finding in COVID-19 Patients
The research team examined blood samples from 178 COVID-19 patients ranging in age from 19 to 88. These individuals had a spectrum of disease severity - from asymptomatic to critical. Using cutting-edge bioinformatics tools - STAR-Fusion, SOAPfuse, and EricScript - the scientists identified over 30,000 chimeric RNA events. However, to ensure reliability, they focused on about 500 high-confidence hybrid transcripts that were detected by more than one software and validated through rigorous filtering methods.
 
Chimeric RNAs are typically associated with cancer, where gene fusion events often give rise to abnormal proteins that drive tumor growth. However, this study found strong evidence that such hybrid RNAs can also emerge in response to viral infections - especially in the case of COVID-19. Surprisingly, over 350 of these chimeric RNAs were found to be specific to SARS-CoV-2 infection, as they were not detected in healthy individuals from previous studies of normal blood transcriptomes.
 
The researchers believe these novel transcripts may be important biomarkers for viral infection and immune response, potentially opening new avenues for diagnosis and understanding disease progression.
 
How Do These Hybrid RNAs Form?
Chimeric RNAs are formed when pieces of genetic material from different genes are mistakenly stitched together during the process of transcribing DNA into RNA. This can happen through several mechanisms - such as transcriptional read-throughs (when RNA polymerase continues reading into a neighboring gene) or through misregulation of normal splicing processes.
 
The study paid special attention to where these hybrid RNA “splice junctions” occurred - either at the start or end of known gene segments (called exons). Interestingly, many of the chimeras found in COVID-19 patients occurred at unexpected places, suggesting the virus may disrupt normal RNA processing.
 
One protein in particular stood out: PTBP1, or polypyrimidine tract-binding protein 1. This RNA-binding protein normally helps regulate the splicing of RNA, but in COVID-19 patients, the loss of PTBP1 function appears to coincide with the production of certain chimeric RNAs. In fact, the researchers showed that when PTBP1 was experimentally reduced in lab-grown blood cells, the same strange hybrid RNAs observed in COVID-19 patients began to appear.
 
Do These Chimeras Mean Anything Clinically?
Yes - and perhaps more than previously thought. The researchers used statistical analyses to correlate the presence of certain chimeric RNAs with COVID-19 disease severity, age, and sex. Remarkably, some chimeric transcripts were more common in asymptomatic individuals, while others appeared more frequently in severe and critical patients.
 
Two chimeric RNAs, dubbed OS (ODF3B-SCO2) and TS (TYMP-SCO2), stood out as particularly significant. These were observed more often in asymptomatic patients and were strongly associated with the loss of PTBP1 activity. When scientists suppressed PTBP1 in erythroid cells derived from human stem cells, these same transcripts were generated. This finding suggests that PTBP1 may act as a molecular switch whose malfunction allows the creation of these abnormal transcripts.
 
Further analysis revealed that many of the genes contributing to these chimeric RNAs are involved in key immune and metabolic processes, such as intracellular transport, energy generation, and oxidative stress response. Some genes were also linked to red blood cell development and neuronal functions, hinting at a potential connection to COVID-related neurological and hematological symptoms.
 
Unique to COVID-19 and Not Seen in Healthy Individuals
The most compelling aspect of the study is that a vast majority of these hybrid RNAs were absent in the blood of healthy individuals, as evidenced by comparison to data from the GTEx (Genotype-Tissue Expression) project. This means these chimeric RNAs are likely not random background events, but instead represent a pathological response to SARS-CoV-2 infection.
 
In one analytical technique called UMAP (Uniform Manifold Approximation and Projection), the researchers were able to distinguish asymptomatic patients from those with symptoms based purely on the patterns of chimeric RNA expression. This reinforces the idea that these hybrid transcripts could serve as a new class of diagnostic or prognostic biomarkers.
 
Experimental Confirmation of the Findings
To further validate their computational predictions, the team selected several of these hybrid RNAs and tested them using laboratory techniques. They successfully confirmed the existence of at least 10 chimeric transcripts through PCR and Sanger sequencing - providing solid experimental evidence that these unusual RNAs are not just theoretical artifacts, but real molecular phenomena present in the blood of COVID-19 patients.
 
The Role of PTBP1 and the Immune System
What makes PTBP1 especially intriguing is its known role in other viral infections. Previous studies have shown that viruses like influenza and other coronaviruses interact with this protein to manipulate host RNA machinery. In this study, the researchers found PTBP1 binding motifs near the splice junctions of the hybrid RNAs - suggesting that SARS-CoV-2 may indirectly control the splicing process through PTBP1 dysfunction.
 
Moreover, when PTBP1 was suppressed in stem-cell-derived red blood cells, the resulting cells not only produced the same chimeric RNAs found in asymptomatic COVID-19 patients but also showed increased expression of interferon-stimulated genes - key players in the antiviral immune response.
 
Conclusions and Future Implications
This remarkable discovery reveals that COVID-19 does far more than just trigger an inflammatory storm or cause respiratory failure. It seems to hijack the very blueprint of how human cells create RNA - resulting in thousands of unusual hybrid transcripts never seen before. These chimeric RNAs might play key roles in immune response, viral replication, or even long-term complications like “Long COVID.”
 
While many of these newly discovered transcripts still need to be fully characterized, they represent a fascinating new layer of complexity in how our bodies respond to viral infections. They may soon serve as early indicators of disease, help predict patient outcomes, or even become targets for novel therapeutic interventions.
 
Importantly, this work also showcases the power of next-generation RNA sequencing in uncovering hidden layers of gene regulation - offering a fresh perspective on host-virus interactions. With further research, these chimeric RNAs might one day guide personalized treatment strategies for COVID-19 and other emerging infectious diseases.
 
The study findings were published in the peer reviewed journal: Genes & Diseases
https://www.sciencedirect.com/science/article/pii/S2352304224001454
 
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