The human immune system is manipulated by SARS-CoV-2, which results in the generation of non-essential proteins, slowing down antiviral immunity, according to scientists.
This groundbreaking research by teams from top Brazilian universities draws attention to potential targets for new COVID-19 treatments, as it underscores the importance of returning infected cells to normal RNA processing.
The coronavirus known as SARS-CoV-2 can bypass the immune response of the human host by utilizing defense cell machinery to induce expression of unproductive isoforms of important antiviral genes.
Coronaviruses and other viruses have the ability to disrupt messenger RNA (mRNA) splicing in order to manipulate protein production, but SARS-CoV-2 employs a similar process to block interferon-mediated transcription, thereby modulating specific immune cells. There is limited information on how this process progressed in COVID-19 as well as other viruses.
The researchers, aided by FAPESP, took on the task of verifying the hypothesis in the scientific literature that the formation of unstable mRNA isoforms can generate non-reactive proteins.
They analyzed the infected host cell landscape through an integrative approach, combining multiple datasets on transcriptomic and proteomic data to create a comprehensive study that followed a multidimensional approach.
Unproductive splicing is classement in major genes associated with the immune system222 and antiviral response222, especially unproductive splicing isoforms produced by SARS-CoV-2 infection, were also characterized as producing fewer "normal" proteins, which were more reactive to viral proteins.
In comparison, inflammatory cytokine and chemokine genes (like IL6, CXCL8, and TNF) predominantly generated productive splicing sequences in response to infection.
The use of public data was chosen by Glória Regina Franco, a full professor at UFMG, who explained that COVID-19 is the first time a viral strategy has been demonstrated at the molecular level, despite the publication of over 50 papers on transcriptomics.
Helder Takashi Imoto Nakaya, a senior researcher at HIAE, is the penultimate author of the study, who believes that this exposes crucial information about potential antiviral medications and immunomodulatory interventions by demonstrating how SARS-CoV-2 interacts with the host's splicing machinery. These findings can help develop therapies that restore normal RNA processing during viral infections, for instance.
Nakaya emphasized that despite the end of the COVID-19 pandemic, it is crucial to continue researching new viruses related to the disease. He also noted that the development of SARS-CoV-3 and SARS-CoV-4 viruses is a plausible explanation for why this possibility may be present in later outbreaks.
With COVID being a problem that millions of people worldwide are ignoring, it is imperative that we study the virus's molecular damage further.
International Journal of Molecular Sciences / www.mdpi.com/1422-0067/25/11/5671.
CAPES, CNPq, and PRPq-UFMG were among the sponsors of the study, along with researchers from Indiana University and Michigan State University in the United States.