Physiology and pathophysiology of a human endogenous retrovirus encoded protease that processes disease-relevant cellular proteins

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Approximately 8% of the human genome mass consists of sequences that derive from infections of germ line cells by exogenous retroviruses millions of years ago. So-called human endogenous retroviruses (HERVs) usually acquired numerous mutations due to long-time presence in the genome and no longer encode former retroviral proteins. Exceptions include a protein encoded by the HERV-W group that appears essential for placenta development and various proteins encoded by evolutionarily young loci of the so-called HERV-K(HML-2) group. Many HERVs, including HERV-K(HML-2), are still transcribed in benign conditions and in a deregulated fashion in various diseases. A functional role of HERV expression has been suggested recently for various types of cancer and neurodegenerative diseases. HERV-K(HML-2) encodes a functional protease that typically processes HERV-K(HML-2) Gag protein. We established in our recent research that HERV-K(HML-2) protease does also process numbers of cellular proteins, among them many disease-relevant proteins. Deregulated expression of HERV-K(HML-2) protease accompanied by degradation of disease-relevant cellular proteins therefore may contribute to development of human diseases. In the current research, we will further investigate the role of HERV-K(HML-2) protease by focusing on specific aspects of the cell biology and potential disease relevance of HERV-K(HML-2) protease. Our research will generate additional important data for more specific investigations of cellular consequences of processing of cellular proteins by HERV-K(HML-2) protease.