Project C04

Principal Investigator

Dr. Janna Bigalke

Universität zu Lübeck

C4

PhD candidate

Sairam Dasika


C4

Project Summary

Role of the human cytomegalovirus (HCMV) E3 SUMO ligase pUL69 in virus reactivation

HCMV (Human cytomegalovirus or human herpesvirus 5), a ubiquitous beta-herpesvirus, produces an E3 SUMO ligase named UL69 during latency [1]. 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 [2], transcription transactivation [3], and nucleocytoplasmic shuttling of viral RNAs [4], 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. 

C4

References

  1. De La Cruz-Herrera CF, Shire K, Siddiqi UZ, et al. A genome-wide screen of Epstein-Barr virus proteins that modulate host SUMOylation identifies a SUMO E3 ligase conserved in herpesviruses. PLoS Pathog. 2018 Jul 6;14(7):e1007176. doi:10.1371/journal.ppat.1007176
  2. Lu M, Shenk T. Human cytomegalovirus UL69 protein induces cells to accumulate in G1 phase of the cell cycle. J Virol. 1999 Jan;73(1):676-83. doi:10.1128/JVI.73.1.676-683.1999
  3. Winkler M, aus Dem Siepen T, Stamminger T. Functional interaction between pleiotropic transactivator pUL69 of human cytomegalovirus and the human homolog of yeast chromatin regulatory protein SPT6. J Virol. 2000 Sep;74(17):8053-64. doi: 10.1128/jvi.74.17.8053-8064.2000
  4. Lischka P, Toth Z, Thomas M, et al The UL69 transactivator protein of human cytomegalovirus interacts with DEXD/H-Box RNA helicase UAP56 to promote cytoplasmic accumulation of unspliced RNA. Mol Cell Biol. 2006 Mar;26(5):1631-43. doi: 10.1128/MCB.26.5.1631-1643.2006