Principal Investigator
Dr. Janna Bigalke
Universität zu Lübeck
C4.2
PhD candidate
Jasper Kroes
C4.2
Project Summary
The role of the non-classical deSUMOylase LUNA from HCMV in viral reactivation from latency
The human cytomegalovirus (HCMV) is a ubiquitous beta-herpesvirus which establishes a lifelong latent infection following primary infection. From this latent state, HCMV can reactivate into lytic replication again, but this switch still lacks complete molecular characterization. To enable reactivation, HCMV utilizes a latency-associated gene product called LUNA to disrupt PML (promyelocytic leukemia) bodies by deSUMOylating PML proteins within the nucleus [1-3]. LUNA is the first described viral SUMO-specific cysteine protease and appears to be non-canonical compared to the SUMO proteases in humans [2]. In this project, we aim to fully characterize LUNA’s deSUMOylase ability on the different SUMO isoforms. Furthermore, we seek to elucidate how LUNA functions as a cysteine protease and what non-isopeptidase functions LUNA can perform during reactivation. We will use a combination of techniques from biochemistry, structural biology, protein biophysics and virology to explore how deSUMOylation by LUNA affects the herpesviral life cycle.
C4.2
References
- Bego M, Maciejewski J, Khaiboullina S, Pari G, St Jeor S. Characterization of an antisense transcript spanning the UL81-82 locus of human cytomegalovirus. J Virol. 2005 Sep;79(17):11022-34. doi:10.1128/JVI.79.17.11022-11034.2005.
- Poole EL, Kew VG, Lau JCH, Murray MJ, Stamminger T, Sinclair JH, Reeves MB. A Virally Encoded DeSUMOylase Activity Is Required for Cytomegalovirus Reactivation from Latency. Cell Rep. 2018 Jul 17;24(3):594-606. doi: 10.1016/j.celrep.2018.06.048.
- Keyes LR, Hargett D, Soland M, Bego MG, Rossetto CC, Almeida-Porada G, St Jeor S. HCMV protein LUNA is required for viral reactivation from latently infected primary CD14⁺ cells. PLoS One. 2012;7(12):e52827. doi: 10.1371/journal.pone.0052827.