Interferon type 1 (syn INFα) normally regulates the activity of the immune system. It is produced in macrophages and monocytes, but also in virus-infected cells. The task of interferon is to initiate viral defense by activating the STAT signaling pathway, which induces the transcription of various antiviral genes in the cell nucleus. INFalpha also has other functions in the viral immune defense (1).

It has been known for some time, that certain SARS-Cov proteins can disrupt the immune response (2). At least two virus group-specific proteins, ORF3b and ORF6, and the nucleocapsid (N, also known as ORF9a) have the ability to inhibit IFN1 production (3). As a result, the host's immune response against the virus is less powerful. However, the protein ORF3b of SARS-CoV-2 and related bat and pangolin viruses suppress INF1 induction more effectively than other SARS-CoV.

Conducting a gene analysis, the scientists found out that the anti-IFN1 activity of ORF3b depends on the length of its C-terminus. In contrast to SARS-CoV, the gene structure of ORF3b of SARS-Cov2 has four premature stop codons that lead to the expression of a drastically shortened ORF3b protein.

For their investigations, the researchers were able to isolate an ORF3b with enhanced INF1 inhibition capacity from two severe COVID-19 cases and use it for their cell culture experiments. For functional investigations, the scientists used a human renal cell line (HEK293). They observed the INF1 promoter activity in the cells in the presence of the ORF3b of SARS-CoV-2 and a SARS-CoV for comparison. To detect INF1 activity in the cells, they applied a luciferase reporter assay.

The results contribute to explain the weak interferon response in COVID-19 patients.

Original publication:
Yoriyuki Konno, Izumi Kimura, Keiya Uriu, Masaya Fukushi, Takashi Irie, Yoshio Koyanagi, So Nakagawa, Kei Sato (2020). SARS-CoV-2 ORF3b is a potent interferon antagonist whose activity is further increased by a naturally occurring elongation variant. bioRxiv preprint, https://www.biorxiv.org/content/10.1101/2020.05.11.088179v1#disqus_thread

The function of accessory SARS-Cov2 viruses can be read about here (4).

Sources:
https://www.pharmazeutische-zeitung.de/virales-protein-hemmt-angeborene-immunreaktion-in-vitro-117756/

Further information:
(1) https://flexikon.doccheck.com/de/Interferon-alpha
(2) Peng Zhou, Hongxia Li, Hanzhong Wang, Lin-Fa Wang, Zhengli Shi (2012). Bat Severe Acute Respiratory Syndrome-Like Coronavirus ORF3b Homologues Display Different Interferon Antagonist Activities. J Gene Virol. 2012 Feb;93(Pt 2):275-281. doi: 10.1099/vir.0.033589-0. Epub 2011 Oct 19. https://pubmed.ncbi.nlm.nih.gov/22012463/
(3) https://pubmed.ncbi.nlm.nih.gov/17108024/
(4) https://www.fz-juelich.de/ibi/ibi-7/DE/Forschung/Teams/Willbold/ArbeitsgruppeHaenel/SARS/sars_node.html