Restriction of endogenous retroviruses by chromatin regulators

• Applicant: Professor Dr. Gunnar Schotta
• Subject Area: Cell Biology
• Term: from 2016 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 318290907

Endogenous retroviruses (ERVs) are remnants of retroviral infections during evolution. More than 10% of mammalian genomes are composed of endogenous retroviruses. Cells have developed strategies to sense endogenous retroviruses and to establish a repressive chromatin structure across retroviral sequences preventing their transcription. Presumably, these mechanisms were developed by host cells to restrict exogenous retroviruses, but, during evolution, integration of retroviral genomes made it necessary to apply these mechanisms for silencing of newly integrated retroviral genomes. Interestingly, endogenous retroviruses are not completely silent. For example, during development, activation of retroviral promoters is used to regulate host genes. Other examples include activation of endogenous retroviruses in the context of T-cell independent B cell activation. These examples demonstrate that silencing of endogenous retroviruses can be specifically relieved, dependent of the cell type or exogenous stimuli. Interestingly, these phenomena parallel the end of the latency phase of retroviruses, and, it is not unreasonable to assume that the mechanisms share similar features. The aim of this project is to study the machineries involved in restriction of endogenous retroviruses by establishing repressive chromatin structures. In addition we want to investigate how this machinery is counteracted in response to external stimuli, when cells show specific de-repression of retroviral sequences. We are hopeful that our studies will not only clarify restriction mechanisms of endogenous retroviruses, but may also turn out fruitful for better understanding cell-autonomous sensing and restriction mechanisms of exogenous retroviruses.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1923: Innate Sensing and Restriction of Retroviruses