Project C04

HCMV (Human cytomegalovirus or human herpesvirus 5), a ubiquitous beta-herpesvirus, produces an E3 SUMO ligase named UL69 during latency (De La Cruz-Herrera et.al (2018)). From the latent phase, the virus can reactivate into lytic replication, but the molecular details of this switch are not yet fully understood. UL69 belongs to the conserved ICP27 family of proteins. It is transcribed during the latent stage of the HCMV lifecycle and has exhibited a myriad of functions in HCMV infection including manipulation of host cell cycle (Lu M, et.al 1999), transcription transactivation (Winkler, M et al.2000), and nucleocytoplasmic shuttling of viral RNAs (Lischka, Peter et al.2006), etc. 

In this project, we aim to methodically identify and characterize the SUMO E3 Ligase domain of UL69, delving into its mechanistic intricacies and exploring its contribution to HCMV latency and reactivation. We will use a combination of techniques from biochemistry, structural biology, infection biology, and protein biophysics to elucidate the molecular details of the SUMOylation mechanism and its role in the herpesviral life cycle.