Key viral factors affect the immunity of COVID19 patients

as of October 2020, SARS-CoV-2 had led to a continuing pandemic, with more than 35 million cases reported worldwide and more than 1 million deaths. Compared with SARS-CoV and influenza A viruses, a prominent feature that distinguishes COVID-19 from SARS in immune response is that SARS-CoV-2 has a poor induction effect on type I interferon (IFN). It is important to note that the damaged IFN response is associated with COVID-19 disease. However, the molecular mechanism of inefficient IFN reactions in SARS-CoV-2 infections is not clear.A team at the Institute of Medical Sciences (IMSUT) of the University of Tokyo aimed to identify the viral factors that determine immune activation after SARS-CoV-2 infection and found that the gene ORF3b, encoded by SARS-CoV-2, was an effective IFN antagonist.Lead scientist Keith Sato, associate professor of systemic virology at the Department of Infectious Disease Control, said: "The adverse IFN reaction in PATIENT-19 patients may be due to the effects of orF3b, the product of the virus. Al though SARS-CoV infection can cause acute and severe pneumonia, SARS-CoV-2 infections can be asymptomatic or cause flu-like symptoms such as fever, cough, and fatigue. Moreover, COVID-19, a marker of SARS-CoV-2 infection, is an undesirable inducement of type I interferon (IFN) compared to SARS-CoV and influenza A virus infections. It is important to note that the damaged IFN response is related to the severity of COVID-19. However, the molecular mechanism of inefficient IFN reactions in SARS-CoV-2 infection is not clear.By comparing the genetic sequences of the SARS-CoV-2 encoded gene with that of SARS-CoV, the team found that the gene length of SARS-CoV-2 ORF3b was significantly shorter than that of SARS-CoV ORF3b.Because ORF3b of SARS-CoV is known as an anti-IFN viral antagonist, they hypothesically assume that the difference in the length of the ORF3b gene between SARS-CoV-2 and SARS-CoV may alter its anti-IFN activity and may further explain this difference. Symptoms of both viral infections.Surprisingly, SARS-CoV-2 ORF3b is a more effective IFN antagonist than SARS-CoV ORF3b. Systematic developmental analysis and functional analysis show that SARS-CoV-2-related viruses in bats and rollers also encode shorter ORF3b gene products with strong anti-IFN activity.The characterization of natural SARS-CoV-2 ORF3b variants with enhanced anti-IFN activityIn addition, the authors' analysis of approximately 17,000 SARS-CoV-2 sequences identified a natural variation in which a longer ORF3b reading box was reconstructed. This variant suppresses IFN more effectively than ORF3b of the parent SARS-CoV-2 strain.Therefore, it is important to continue monitoring the virus sequence to see if new ORF3b mutations occur during the current pandemic. (Bio Valley Bioon.com)source: The source of the information: A viral that impairs immune responses in COVID-19 patientsOriginal source: Yoriyuki Konno, Izumi Kimura, Keiya Uriu, Masaya Fukushi, Takashi Irie, Yoshio Koyanagi, Daniel Sauter, Robert J. Gifford, So Nakagawa, Kei Sato. SARS-CoV-2 ORF3b Is a Potent Interferon Antagonist Whose Activity Is Increased by a Naturally Occurring Elongation Variant. Cell Reports, 2020; 32 (12): 108185 DOI: 10.1016/j.celrep.2020.108185