Herpesviruses acquire their membrane envelopes in the cytoplasm of infected cells via a molecular mechanism that remains unclear. Herpes simplex virus (HSV)-1 proteins pUL7 and pUL51 form a complex required for efficient virus envelopment. We show that interaction between homologues of pUL7 and pUL51 is conserved across human herpesviruses, as is their association with trans-Golgi membranes. We characterized the HSV-1 pUL7:pUL51 complex by solution scattering and chemical crosslinking, revealing a 1:2 complex that can form higher-order oligomers in solution, and we solved the crystal structure of the core pUL7:pUL51 heterodimer. While pUL7 adopts a previously-unseen compact fold, the helix-turn-helix conformation of pUL51 resembles the cellular endosomal complex required for transport (ESCRT)-III component CHMP4B and pUL51 forms ESCRT-III-like filaments, suggesting a direct role for pUL51 in promoting membrane scission during virus assembly. Our results provide a structural framework for understanding the role of the conserved pUL7:pUL51 complex in herpesvirus assembly.
Bibliographical note© 2020, Butt et al.
- HEK293 Cells
- HeLa Cells
- Herpes Simplex/virology
- Herpesvirus 1, Human/chemistry
- Models, Molecular
- Protein Binding
- Protein Interaction Domains and Motifs
- Protein Structure, Quaternary
- Protein Structure, Tertiary
- Viral Matrix Proteins/chemistry
- Viral Proteins/chemistry
- Virus Assembly
- Virus Replication
- trans-Golgi Network