Latest SARS-Cov-2 Research: Study Discovers That SARS-CoV-2-Encoded Small RNAs Represses Host Expression Of SERINC5 For Viral Replication.
Latest SARS-CoV-2 Research
: A recent study by researchers from the Centro de Investigación Príncipe Felipe (CIPF), Valencia-Spain, Hospital Universitario de la Ribera, Valencia-Spain, Centro Nacional de Biotecnología (CNB), CSIC, Madrid and Yale School of Medicine, Connecticut-United States, sheds light on how the virus is able to evade the host immune response. Specifically, the researchers found that SARS-CoV-2-encoded small RNAs are able to repress the host expression of SERINC5, a key innate immunity factor that restricts the infectivity of certain viruses, to facilitate viral replication.
The study used a combination of in silico analysis, in vitro experiments, and patient samples to investigate the role of SARS-CoV-2-encoded small RNAs in the regulation of SERINC5. The researchers first analyzed the expression of SERINC5 during SARS-CoV-2 infection in two distinct cell lines and in COVID-19 patient samples. They found that SERINC5 levels were reduced during infection, suggesting that the virus antagonizes SERINC5 activity by downregulating its expression.
Since no viral protein capable of controlling the expression of SERINC5 had been identified, the researchers hypothesized that SARS-CoV-2-encoded small RNAs might be responsible for this repression.
They identified two newly identified small RNAs with predicted binding sites in the 3′-untranslated region (3’-UTR) of the SERINC5 gene. The researchers found that both viral small RNAs can bind the 3’UTR of SERINC5 mRNA, reducing SERINC5 expression in vitro.
Furthermore, the researchers showed that an anti-small RNA treatment to Vero E6 cells before SARS-CoV-2 infection recovered the levels of SERINC5 and reduced the levels of N and S viral proteins. They also found that SERINC5 positively controls the levels of Mitochondrial Antiviral Signaling (MAVS) protein in Vero E6.
These results highlight the therapeutic potential of targeting small RNAs based on their action on key proteins of the innate immune response during SARS-CoV-2 viral infection.
The study also sheds light on the role of small RNAs in virus-host interactions. It has been shown that both DNA and RNA viral genomes can encode non-coding small viral RNAs (svRNAs) like miRNAs. These small RNAs can be considered more strategic than viral proteins in terms of regulation of gene expression due to their small size, their absence of immunogenicity and their multi-target hit with rapid evolution capacity.
Recently, Latest SARS-CoV-2 Research
papers also demonstrated the existence of miRNAs encoded in the SARS-CoV-2 genome and their biological relevance.
Also, by using computational approaches, several studies have predicted the possible existence of vira
l miRNAs with diverse roles in the pathogenicity of this virus.
Moreover, the deep sequencing analysis of small RNAs from lungs of mice infected with severe acute respiratory syndrome coronavirus (SARS-CoV) revealed three 18-22 nt svRNAs originated from the nsp3 and N genomic regions of SARS-CoV. Researchers found that one of them, svRNA-N, contributes to SARS-CoV pathogenesis by regulating the production of proinflammatory cytokines.
However, these small RNAs do not seem to possess the canonical stem-loop structure of miRNAs, and their biogenesis and mechanism of action are not completely clear.
Moe recent studies have emerged recently showing the existence of miRNAs encoded in the SARS-CoV-2 genome and their biological relevance. By using computational approaches, several studies have predicted the possible existence of viral miRNAs with diverse roles in the pathogenicity of this virus.
Overall, the study highlights the importance of understanding the interactions between viruses and host cells, particularly the role of small RNAs in regulating host gene expression. It also provides insights into potential therapeutic targets for COVID-19, such as small RNAs, and the potential use of biomarkers in the diagnosis of the disease.
The study findings were published in the peer reviewed journal: Frontiers in Microbiology.
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