As of October 2020, SARS-CoV-2 has caused a continuous pandemic, with more than 35 million cases reported worldwide and more than 1 million deaths. Compared with SARS-CoV and influenza A viruses, a superior feature that distinguishes COVID-19 from SARS in terms of immune response is the low induction rate of SARS-CoV-2 type I interferon (IFN). It is worth noting that the weakened IFN response is related to COVID-19 disease. However, the molecular mechanism of the ineffective IFN response in SARS-CoV-2 infection remains unclear.
The research team of the University of Tokyo Institute of Medical Sciences (IMSUT) aims to determine the viral factors encoded by SARS-CoV-2 that determine immune activation after SARS-CoV-2 infection. We have found that the gene ORF3b is an effective IFN antagonist. .. Chief Scientist Keiji Sato, Associate Professor of Systemic Virology, Division of Infectious Disease Control, said: "The poor IFN response of COVID-19 patients may be due to the role of this virus product ORF3b."
SARS-CoV infection is acute and severe pneumonia, but SARS-CoV-2 infection is asymptomatic or can cause flu-like symptoms such as fever, cough and fatigue. In addition, compared with SARS-CoV and influenza A virus infections, a sign of SARS-CoV-2 infection, COVID-19 has insufficient ability to induce type I interferon (IFN). It is worth noting that the impaired IFN response is related to the severity of COVID-19. However, the molecular mechanism of the ineffective IFN response in SARS-CoV-2 infection remains unclear. By comparing the gene sequences of SARS-CoV-2 and SARS-CoV, the researchers found that the gene length of SARS-CoV-2ORF3b was significantly shorter than that of SARS-CoVORF3b. SARS-CoV ORF3b is known as an anti-IFN virus antagonist, so the difference in ORF3b gene length between SARS-CoV-2 and SARS-CoV may change its anti-IFN activity and further explain. They think there is such a difference. Symptoms of these two viruses. Surprisingly, SARS-CoV-2ORF3b is a more effective IFN antagonist than SARS-CoVORF3b. Phylogenetic and functional analysis showed that SARS-CoV-2 related viruses in bats and pangolins also encode shorter ORF3b gene products with strong anti-IFN activity. Characterization of natural SARS-CoV-2 ORF3b variants with enhanced anti-IFN activity. In addition, the author's analysis of approximately 17,000 SARS-CoV-2 sequences reconstructed longer natural variants of ORF3b. It has been identified. Reading frame. This variant inhibits IFN more effectively than the parent SARS-CoV-2 strain ORF3b.
Therefore, it is important to continue to monitor the virus sequence to see if new ORF3b mutations appear during the current pandemic.