Structure of the herpes-simplex virus portal-vertex

McElwee, M., Vijayakrishnan, S. , Rixon, F. and Bhella, D. (2018) Structure of the herpes-simplex virus portal-vertex. PLoS Biology, 16(6), e2006191. (doi:10.1371/journal.pbio.2006191) (PMID:29924793) (PMCID:PMC6028144)

McElwee, M., Vijayakrishnan, S. , Rixon, F. and Bhella, D. (2018) Structure of the herpes-simplex virus portal-vertex. PLoS Biology, 16(6), e2006191. (doi:10.1371/journal.pbio.2006191) (PMID:29924793) (PMCID:PMC6028144)

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Abstract

Herpesviruses include many important human pathogens such as herpes simplex virus, cytomegalovirus, varicella-zoster virus, and the oncogenic Epstein–Barr virus and Kaposi sarcoma–associated herpesvirus. Herpes virions contain a large icosahedral capsid that has a portal at a unique 5-fold vertex, similar to that seen in the tailed bacteriophages. The portal is a molecular motor through which the viral genome enters the capsid during virion morphogenesis. The genome also exits the capsid through the portal-vertex when it is injected through the nuclear pore into the nucleus of a new host cell to initiate infection. Structural investigations of the herpesvirus portal-vertex have proven challenging, owing to the small size of the tail-like portal-vertex–associated tegument (PVAT) and the presence of the tegument layer that lays between the nucleocapsid and the viral envelope, obscuring the view of the portal-vertex. Here, we show the structure of the herpes simplex virus portal-vertex at subnanometer resolution, solved by electron cryomicroscopy (cryoEM) and single-particle 3D reconstruction. This led to a number of new discoveries, including the presence of two previously unknown portal-associated structures that occupy the sites normally taken by the penton and the Ta triplex. Our data revealed that the PVAT is composed of 10 copies of the C-terminal domain of pUL25, which are uniquely arranged as two tiers of star-shaped density. Our 3D reconstruction of the portal-vertex also shows that one end of the viral genome extends outside the portal in the manner described for some bacteriophages but not previously seen in any eukaryote viruses. Finally, we show that the viral genome is consistently packed in a highly ordered left-handed spool to form concentric shells of DNA. Our data provide new insights into the structure of a molecular machine critical to the biology of an important class of human pathogens.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Rixon, Dr Frazer and Bhella, Professor David and McElwee, Dr Marion and Vijayakrishnan, Dr Swetha
Authors: McElwee, M., Vijayakrishnan, S., Rixon, F., and Bhella, D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS Biology
Publisher:Public Library of Science
ISSN:1544-9173
ISSN (Online):1545-7885
Copyright Holders:Copyright © 2018 McElwee et al.
First Published:First published in PLoS Biology 16(6): e2006191
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656541Structural studies of human viruses and host interactionsDavid BhellaMedical Research Council (MRC)MC_UU_12014/7MVLS III - CENTRE FOR VIRUS RESEARCH