COVID-19 News: Researchers Discover That SARS-CoV-2 Infection Activates Endogenous Retroviruses Of The LTR69 Subfamily

COVID-19 News: Scientists from the Institute for Stem Cell Science and Regenerative Medicine, Bangalore-India, Institute for Medical Virology and Epidemiology of Viral Diseases at the University Hospital Tübingen-Germany, Department of Molecular Biology and Genetics at Cornell University-USA and the German Center for Neurodegenerative Diseases (DZNE)-Germany have in a new study found that SARS-CoV-2 infection activates endogenous retroviruses of the LTR69 sub-family.


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Past COVID-19 News coverages have already showed that COVID-19 infections could activate various endogenous retroviruses (ERVs) or dormant retrotransposons and these play an important role in the host response to infection and the development of disease.
https://www.thailandmedical.news/news/breaking-covid-19-news-study-discovers-that-sars-cov-2-modulates-human-endogenous-retrovirus-herv-transcriptome-during-infection
 
https://www.thailandmedical.news/news/breaking-sars-cov-2-infection-induces-human-endogenous-retrovirus-type-w-envelope-protein-expression-in-blood-lymphocytes-and-tissues
 
The study team by combining RNA- and ChIP-sequencing analyses with RT-qPCR, showed that COVID-19 infection induces the LTR69 subfamily of ERVs, both in vitro and in vivo.
 
Utilizing functional assays, the study team identified one SARS-CoV-2-activated LTR69 locus, termed Dup69, which exhibits enhancer activity and is responsive to the transcription factors IRF3 and p65/RelA.
 
LTR69-Dup69 is located about 500 bp upstream of a long non-coding RNA gene (ENSG00000289418) and within the PTPRN2 gene encoding a diabetes-associated autoantigen.
 
Worryingly, both ENSG00000289418 and PTPRN2 showed a significant increase in expression upon SARS-CoV-2 infection.
 
The study findings shed light on the interplay of exogenous with endogenous viruses and helps to understand how ERVs regulate gene expression during infection.
 
The study findings were published on a preprint server and are currently being peer reviewed.
https://www.biorxiv.org/content/10.1101/2023.03.21.533610v1
 
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the COVID-19 pandemic, has had an enormous impact on worldwide health and the economy. This virus has infected billions of people and caused millions of deaths. There is an urgent need to better understand how the virus interacts with the cells it infects and how it causes the disease.
 
Recent research has suggested that spe cific DNA sequences, known as transposable elements (TEs), play a critical role in how our bodies respond to viral infections and how diseases develop. For example, some TEs can help control the production of proteins that fight against viruses or other host proteins. Additionally, TEs can be detected by our cells' sensors, which then trigger immune responses to help fight off the infection.
 
Transposable elements (TEs) are sections of DNA that can move around within our genetic code. They come in many different forms and sizes, from 100 to 10,000 base pairs or more. There are two main types of TEs, and they are categorized based on how they move within the genome.
 
Class 1 elements, called retrotransposons, use a "copy-and-paste" method. They first change into RNA and then back into DNA before inserting themselves into a new location in the genome. Some of these retrotransposons work similarly to how retroviruses do when they integrate into our DNA. For long terminal repeat (LTR) retrotransposons, integration occurs by means of a cleavage and strand-transfer reaction catalyzed by an integrase much like retroviruses.
 
Some viruses, such as HIV, human cytomegalovirus (HCMV), and influenza A virus (IAV), can activate certain TEs that are usually not active.

In this study, researchers used publicly available data from infected cell lines and samples from patients to better understand the effect of SARS-CoV-2 on the activity of TEs in cells exposed to the virus.
 
The study team found that SARS-CoV-2 infection activates a specific group of endogenous retroviruses (ERVs), which are called LTR69 repeats. These repeats are part of the HERV-L family of endogenous retroviruses. The researchers also identified a specific LTR69 repeat that acts as a control switch, activated by certain proteins when cells detect viral RNA.
 
Human endogenous retroviruses (HERVs) are like "fossil viruses" within our DNA, making up about 8% of our genome. They come from past retroviral infections and are passed down through generations. HERVs have a structure similar to current retroviruses, like HIV. They contain three main regions (gag, pol, and env) and two long terminal repeats (LTRs), which help regulate gene expression. The gag and env genes create capsid and envelope proteins, while the pol gene makes enzymes needed for the virus to replicate and integrate. Some HERVs might have given us biological benefits, but others have been linked to cancers and autoimmune diseases.
 
To determine the effect of SARS-CoV-2 infection on the activity of TEs, the researchers analyzed data from cell lines and COVID-19 patients. The study team found that LTR69 expression was increased in cells infected with SARS-CoV-2, and that this increase was also seen in lung cells and fluid samples from deceased and non-deceased COVID-19 patients.
 
The study team then tested whether some of the activated LTR69 repeats could regulate other parts of the DNA. They found that one specific LTR69 repeat, called LTR69-Dup69, had an enhancing effect on a nearby gene. This repeat is located close to a long non-coding RNA gene and a gene that codes for a protein involved in type 1 diabetes. The researchers found that the expression of both of these genes was increased in cells infected with SARS-CoV-2.
 
The researchers then looked at the mechanisms behind the activation of LTR69-Dup69 and found that it was responsive to specific proteins activated in infected cells.
 
The study team concluded that the LTR69 repeat is activated in SARS-CoV-2 infected cells and may play a role in controlling the expression of nearby genes.
 
However, the study team acknowledged that their study has limitations, including the small sample sizes used, and suggested that future research should focus on confirming these findings in larger datasets and determining the exact role of LTR69 in the context of viral infections.
 
For the latest COVID-19 News, keep on logging to Thailand Medical News.
 
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