A team of researchers at the Indian Institute of Science (IISc) has identified a protein in the SARS-CoV-2, the virus behind Covid-19, that antagonises the host’s immune system.In the study, published in the journal Cellular and Molecular Life Sciences, the team identified a viral protein called ORF6, which blocks immunity.
During Covid infection, the body’s early antiviral responses are orchestrated by Interferons (IFNs), triggering specific signalling events that pose a critical hurdle for viruses.Among the identified proteins, ORF6 was found as the most potent inhibitor of IFN induction and signaling.
The researchers led by Oyahida Khatun, Mansi Sharma, and others from the Center for Infectious Disease Research (CIDR) at IISc, showed that the protein paralyses cellular innate immunity through multiple mechanisms.
While consistent with previous research on ORF6 function, the study provided evidence that ORF6 directly interacts with a specific host viral sensor called RIG-I, responsible for recognising viral RNA in infected cells.The presence of the SARS-CoV-2 ORF6 protein resulted in reduced levels of RIG-I and the degradation of an enzyme called TRIM25, crucial for activating RIG-I and controlling viral infection.
Consequently, ORF6 also obstructed the expression of antiviral genes downstream of RIG-I by blocking the nuclear import of transcription factors involved in this process.This is analogous to disabling the ignition (RIG-I) and applying the brakes (inhibiting antiviral gene expression) to halt the cellular antiviral response.
Furthermore, the researchers proposed the possibility of removing genes coding for ORF6 and other IFN antagonists from the SARS-CoV-2 viral genome as a potential strategy for developing live vaccines.