Die Rolle der TRIM-Protein-Familie und anderer Wirtszellfaktoren bei der Restriktion von SARS-CoV-2
Zusammenfassung der Projektergebnisse
The pandemic caused by the SARS-CoV-2 coronavirus has infected over 600 million people worldwide. More than 6.5 million people have officially died in connection with the virus. Vaccination is the best and most effective, but not complete, protection against severe or fatal COVID-19. Early treatment has emerged as a possibility to dramatically mitigate infection and prevent many hospitalizations and deaths. Nevertheless, the virus constantly evades the human immune system via new mutations, and prevention or therapy are not available in all places. SARS-CoV-2 can infect different cell types, and apart from the formation of antibodies or T-cells, infected cells in the organism also defend themselves independently with innate mechanisms. The family of TRIM proteins is tightly involved in cellular restriction and innate defense. This project used suppression and overexpression experiments to study the role of various TRIM proteins and other cellular factors in SARS-CoV-2 infection. A screening system with siRNA mediated gene knockdown against more than 80 cellular factors in different cell types has been successfully established. In particular, the influence on the speed or efficiency of virus replication was be investigated using self-developed, optimized marker viruses. Thereby we identified TRIM family proteins both as restrictive and promoting factors of SARS-CoV-2 infection. In the further course, these identified factors are currently analysed for their exact mode of action in relation to the infection. In particular, the mechanism by which the restrictive or promoting effect is achieved is be elucidated. In perspective, this will result in new targets for antiviral therapy.
Projektbezogene Publikationen (Auswahl)
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Cloning of a Passage-Free SARS-CoV-2 Genome and Mutagenesis Using Red Recombination. International Journal of Molecular Sciences, 22(19), 10188.
Herrmann, Alexandra; Jungnickl, Doris; Cordsmeier, Arne; Peter, Antonia Sophia; Überla, Klaus & Ensser, Armin
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Methodological Development of a Multi-Readout Assay for the Assessment of Antiviral Drugs against SARS-CoV-2. Pathogens, 10(9), 1076.
Hahn, Friedrich; Häge, Sigrun; Herrmann, Alexandra; Wangen, Christina; Kicuntod, Jintawee; Jungnickl, Doris; Tillmanns, Julia; Müller, Regina; Fraedrich, Kirsten; Überla, Klaus; Kohlhof, Hella; Ensser, Armin & Marschall, Manfred
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SMYD2 Inhibition Downregulates TMPRSS2 and Decreases SARS-CoV-2 Infection in Human Intestinal and Airway Epithelial Cells. Cells, 11(8), 1262.
Yu, Yu-Qiang; Herrmann, Alexandra; Thonn, Veronika; Cordsmeier, Arne; Neurath, Markus F.; Ensser, Armin & Becker, Christoph
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Viral Mimicry of Interleukin-17A by SARS-CoV-2 ORF8. mBio, 13(2).
Wu, Xin; Xia, Tian; Shin, Woo-Jin; Yu, Kwang-Min; Jung, Wooram; Herrmann, Alexandra; Foo, Suan-Sin; Chen, Weiqiang; Zhang, Pengfei; Lee, Jong-Soo; Poo, Haryoung; Comhair, Suzy A. A.; Jehi, Lara; Choi, Young Ki; Ensser, Armin & Jung, Jae U.
