Assembly of infectious Kaposi's sarcoma-associated herpesvirus progeny requires formation of a pORF19 pentamer.
Animals
Capsid
/ chemistry
Conserved Sequence
Crystallography, X-Ray
DNA Packaging
DNA, Viral
/ genetics
Drosophila
HEK293 Cells
Herpesvirus 8, Human
/ physiology
Humans
Models, Molecular
Mutagenesis
/ genetics
Mutant Proteins
/ metabolism
Open Reading Frames
/ genetics
Protein Multimerization
Viral Proteins
/ chemistry
Virus Assembly
/ physiology
Journal
PLoS biology
ISSN: 1545-7885
Titre abrégé: PLoS Biol
Pays: United States
ID NLM: 101183755
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
19
01
2021
accepted:
22
09
2021
entrez:
4
11
2021
pubmed:
5
11
2021
medline:
22
12
2021
Statut:
epublish
Résumé
Herpesviruses cause severe diseases particularly in immunocompromised patients. Both genome packaging and release from the capsid require a unique portal channel occupying one of the 12 capsid vertices. Here, we report the 2.6 Å crystal structure of the pentameric pORF19 of the γ-herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) resembling the portal cap that seals this portal channel. We also present the structure of its β-herpesviral ortholog, revealing a striking structural similarity to its α- and γ-herpesviral counterparts despite apparent differences in capsid association. We demonstrate pORF19 pentamer formation in solution and provide insights into how pentamerization is triggered in infected cells. Mutagenesis in its lateral interfaces blocked pORF19 pentamerization and severely affected KSHV capsid assembly and production of infectious progeny. Our results pave the way to better understand the role of pORF19 in capsid assembly and identify a potential novel drug target for the treatment of herpesvirus-induced diseases.
Identifiants
pubmed: 34735435
doi: 10.1371/journal.pbio.3001423
pii: PBIOLOGY-D-21-00173
pmc: PMC8568140
doi:
Substances chimiques
DNA, Viral
0
Mutant Proteins
0
Viral Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e3001423Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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