The role of TRIM-family proteins and other host cell factors in the restriction of SARS-CoV-2

• Applicant: Professor Dr. Armin Ensser
• Subject Area: Virology
• Term: from 2021 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 458681345

We postulate that hitherto unidentified TRIM proteins play critical roles in restricting Betacoronavirus host susceptibility and lytic replication. Coronavirus infection is characterized by productive viral replication. Molecular insight into the factors that modulate the susceptibility to lytic replication is of fundamental importance, in particular also with respect to obvious gender-related differences. Although major progress has been made towards identifying the viral factors that regulate virus attachment and fusion, our knowledge of host intrinsic factors that modulate replication is still rudimentary. Tripartite motif (TRIM) proteins are increasingly recognized as important antiviral (and also proviral) factors that modulate the replication of a wide range of RNA viruses and DNA viruses. TRIM proteins can inhibit viral replication by either directly targeting viral components or modulating the innate immune responses that result in antiviral gene expression. The mechanism of antiviral restriction often relies in the TRIM E3 ligase functions, which target viral or host proteins for proteasomal degradation. As another example, TRIM19 (also known as promyelocytic leukaemia protein, PML) restricts multiple RNA viruses and DNA viruses, by organizing PML nuclear bodies, in particular also in response to interferons [reviewed in 5, 6]. We will 1) identify TRIM family proteins restricting SARS-CoV-2, and 2) start to delineate the mechanism of identified SARS-CoV-2-restricting TRIMs. Using a replicon-marker system, which was developed in our lab and 3) CRISPR knockout will point out directions for continued research projects. If our study identifies a role of a TRIM protein in intrinsic immunity and host cell interaction against Coronavirus infection, this may be targeted for therapeutic intervention.

• DFG Programme: Research Grants