| Autor: |
van Huizen M; Molecular Virology Laboratory, Leiden University Center of Infectious Diseases (LU-CID), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., Vendrell XM; Molecular Virology Laboratory, Leiden University Center of Infectious Diseases (LU-CID), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., de Gruyter HLM; Molecular Virology Laboratory, Leiden University Center of Infectious Diseases (LU-CID), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., Boomaars-van der Zanden AL; Molecular Virology Laboratory, Leiden University Center of Infectious Diseases (LU-CID), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., van der Meer Y; Molecular Virology Laboratory, Leiden University Center of Infectious Diseases (LU-CID), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., Snijder EJ; Molecular Virology Laboratory, Leiden University Center of Infectious Diseases (LU-CID), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., Kikkert M; Molecular Virology Laboratory, Leiden University Center of Infectious Diseases (LU-CID), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., Myeni SK; Molecular Virology Laboratory, Leiden University Center of Infectious Diseases (LU-CID), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands. |
| Abstrakt: |
Mitochondrial antiviral signaling protein (MAVS) is a crucial signaling adaptor in the sensing of positive-sense RNA viruses and the subsequent induction of the innate immune response. Coronaviruses have evolved multiple mechanisms to evade this response, amongst others, through their main protease (M pro ), which is responsible for the proteolytic cleavage of the largest part of the viral replicase polyproteins pp1a and pp1ab. Additionally, it can cleave cellular substrates, such as innate immune signaling factors, to dampen the immune response. Here, we show that MAVS is cleaved in cells infected with Middle East respiratory syndrome coronavirus (MERS-CoV), but not in cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This cleavage was independent of cellular negative feedback mechanisms that regulate MAVS activation. Furthermore, MERS-CoV M pro expression induced MAVS cleavage upon overexpression and suppressed the activation of the interferon-β (IFN-β) and nuclear factor-κB (NF-κB) response. We conclude that we have uncovered a novel mechanism by which MERS-CoV downregulates the innate immune response, which is not observed among other highly pathogenic coronaviruses. |
