Using cell cultures, the research team studied the impact of SARS-CoV-2 proteins on the interferon (IFN) response and autophagy, a recycling program in which damaged or misfolded proteins are degraded (1).

In their studies, a group of signaling proteins released by the host cell in response to the presence of viruses played a significant role. Interferons are classified into three classes based on their biological activity, gene structure, and the cells by which they are produced. Type I interferons consist of the signaling proteins IFNα and IFNβ, and the less-studied IFNω, IFNκ, and IFNτ. Type II interferons consist of IFNγ, which is produced primarily by activated NK cells or T cells but not by virus-infected cells (2). The type III interferon group consists of four IFN-λ (lambda) molecules. Intestinal epithelial cells (IECs) respond almost exclusively to type III IFNs (3).

SARS-Cov-2 viral proteins have a differential impact on the signaling pathways of the different types.  Researchers observed that SARS-CoV-2 proteins counteract autophagy and type I IFN more efficiently than type II or III IFN signaling. Infection experiments confirmed the potent inhibition of SARS-Cov-2 signaling proteins by IFN-γ (interferon type II) and -λ1 (interferon type III).

The researchers concluded that there is a vulnerability of the SARS-Cov-2 virus to type II and III interferons, which could contribute to the development of safe and effective antiviral approaches.


Original publication:
Hayn, M., Hirschenberger, M., Koepke, L., et al (2021). Systematic Functional Analysis of SARS-CoV-2 Proteins Uncovers Viral Innate Immune Antagonists and.
Remaining Vulnerabilities. Cell Reports 27 April 2021, doi.org/10.1016/j.celrep.2021.109126.

Sources:
https://idw-online.de/de/news768198

Further:
(1) Lenzen-Schulte, M. & Zylka-Menhorn, V. (2016). Autophagy: "self-mutilation" as a survival strategy. Deutsches Ärzteblatt 113/40: A-1740/B-1469/C-1461 https://www.aerzteblatt.de/archiv/182779/Autophagie-Selbstverstuemmelung-als-Ueberlebensstrategie
(2) Mergler, J. (2008). Functionality of the interferon typeI and typeII pathway in Burkitt's lymphoma cells. Dissertation LMU Munich. https://edoc.ub.uni-muenchen.de/8940/1/Mergler_Judith.pdf
(3) Sergei V. Kotenko, S. V. & Durbin, J. E. (2017). Contribution of type III interferons to antiviral immunity: location, location, location. journal of Biological
Chemistry 292/18: P7295-7303. https://www.jbc.org/article/S0021-9258(20)42844-3/fulltext.