SV40 Large T Antigen Is Not Responsible for the Loss of STING in 293T Cells but Can Inhibit cGAS-STING Interferon Induction
| Autor: | Efrem S. Lim, Guillermo S. Trivino-Soto, Lily I. Wu, Joshua B. Reus, Kristiana Kokott |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Transcriptional Activation Transcription Genetic viruses Antigens Polyomavirus Transforming Amino Acid Motifs lcsh:QR1-502 macromolecular substances Biology Origin of replication lcsh:Microbiology Article 03 medical and health sciences 0302 clinical medicine Plasmid Immune system Interferon Virology medicine Humans Promoter Regions Genetic musculoskeletal neural and ocular physiology HEK 293 cells Membrane Proteins DNA virus Transfection interferon Interferon-beta Nucleotidyltransferases eye diseases 3. Good health Cell biology Sting large T antigen 030104 developmental biology Infectious Diseases HEK293 Cells nervous system Gene Expression Regulation 293T 030217 neurology & neurosurgery medicine.drug SV40 polyomavirus cGAS STING |
| Zdroj: | Viruses Viruses, Vol 12, Iss 2, p 137 (2020) Volume 12 Issue 2 |
| ISSN: | 1999-4915 |
| Popis: | Several DNA viruses have evolved antagonists to inhibit the cyclic GMP&ndash AMP synthase (cGAS)-stimulator of interferon genes (STING) DNA-sensing immune pathway. This includes DNA viral oncogenes that antagonize the cGAS-STING pathway by binding STING through the LxCxE motif. The 293T human cells are widely used in biology studies as they are highly transfectable. While parental 293 cells express high levels of STING, 293T cells lack STING and are unable to induce interferon antiviral responses to cytosolic DNA. Additionally, 293T cells express the SV40 polyomavirus large T antigen (LT) which enhances the replication of transfected DNA plasmids carrying the SV40 origin of replication. Since SV40 LT also encodes the LxCxE motif, the lack of STING expression in 293T cells is commonly assumed to be due to SV40 large T antigen. We find that SV40 LT does not alter exogenously expressed and endogenous levels of STING protein. We show that STING transcription is suppressed in 293T cells but is not driven by SV40. This study also revealed that SV40 LT does indeed inhibit cGAS-STING interferon induction, but through a mechanism distinct from other DNA virus oncogenes. Collectively, these results indicate that while SV40 LT can inhibit cGAS-STING interferon induction, it does so in an unanticipated manner. |
| Databáze: | OpenAIRE |
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