The SUMOylation of Human Cytomegalovirus Capsid Assembly Protein Precursor (UL80.5) Affects Its Interaction with Major Capsid Protein (UL86) and Viral Replication

Viruses. 2023 Apr 7;15(4):931. doi: 10.3390/v15040931.

Abstract

Human Cytomegalovirus Capsid Assembly Protein Precursor (pAP, UL80.5) plays a key role in capsid assembly by forming an internal protein scaffold with Major Capsid Protein (MCP, UL86) and other capsid subunits. In this study, we revealed UL80.5 as a novel SUMOylated viral protein. We confirmed that UL80.5 interacted with the SUMO E2 ligase UBC9 (58-93aa) and could be covalently modified by SUMO1/SUMO2/SUMO3 proteins. 371Lysine located within a ψKxE consensus motif on UL80.5 carboxy-terminal was the major SUMOylation site. Interestingly, the SUMOylation of UL80.5 restrained its interaction with UL86 but had no effects on translocating UL86 into the nucleus. Furthermore, we showed that the removal of the 371lysine SUMOylation site of UL80.5 inhibited viral replication. In conclusion, our data demonstrates that SUMOylation plays an important role in regulating UL80.5 functions and viral replication.

Keywords: SUMOylation; UL80.5; capsid assembly; human cytomegalovirus (HCMV).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Capsid Proteins* / genetics
  • Capsid Proteins* / metabolism
  • Capsid* / metabolism
  • Cytomegalovirus / metabolism
  • Humans
  • Lysine / metabolism
  • Protein Precursors
  • Small Ubiquitin-Related Modifier Proteins / metabolism
  • Sumoylation
  • Viral Proteins / genetics
  • Virus Replication

Substances

  • Capsid Proteins
  • Lysine
  • Viral Proteins
  • Small Ubiquitin-Related Modifier Proteins
  • Protein Precursors

Grants and funding

This research was funded by the National Natural Science Foundation of China (82100468, 31500137), the Department of Science and Technology of Hubei Province (2021CFB229), and the Department of Education of Hubei Province (Q20212006).