Electron microscopy mapping of the DNA-binding sites of monomeric, dimeric, and multimeric KSHV RTA protein

J Virol. 2023 Oct 31;97(10):e0063723. doi: 10.1128/jvi.00637-23. Epub 2023 Sep 26.

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is a human herpesvirus associated with several human cancers, typically in patients with compromised immune systems. Herpesviruses establish lifelong infections in hosts in part due to the two phases of infection: the dormant and active phases. Effective antiviral treatments to prevent the production of new viruses are needed to treat KSHV. A detailed microscopy-based investigation of the molecular interactions between viral protein and viral DNA revealed how protein-protein interactions play a role in DNA-binding specificity. This analysis will lead to a more in-depth understanding of KSHV DNA replication and serve as the basis for anti-viral therapies that disrupt and prevent the protein-DNA interactions, thereby decreasing spread to new hosts.

Keywords: HHV-8; KSHV; electron microscopy; human herpesviruses; viral replication.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Binding Sites
  • DNA, Viral* / chemistry
  • DNA, Viral* / metabolism
  • DNA, Viral* / ultrastructure
  • Herpesvirus 8, Human* / chemistry
  • Herpesvirus 8, Human* / metabolism
  • Herpesvirus 8, Human* / ultrastructure
  • Humans
  • Microscopy, Electron*
  • Protein Binding
  • Protein Interaction Maps
  • Protein Multimerization*
  • Sarcoma, Kaposi / virology
  • Substrate Specificity
  • Trans-Activators* / chemistry
  • Trans-Activators* / metabolism
  • Trans-Activators* / ultrastructure
  • Virus Replication / genetics

Substances

  • DNA, Viral
  • ORF 50 transactivator
  • Rta protein, Human herpesvirus 8
  • Trans-Activators