Structural basis for capsid recruitment and coat formation during HSV-1 nuclear egress.

Elizabeth B Draganova,Jiayan Zhang,Z Hong Zhou,Ekaterina E Heldwein

doi:10.7554/elife.56627

Elizabeth B Draganova, Jiayan Zhang + Show 2 more

Open Access

https://doi.org/10.7554/elife.56627

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Journal: eLife	Publication Date: Jun 24, 2020
Citations: 32	License type: CC BY 4.0

Affiliation: Tufts University, University of California, Los Angeles

Abstract

During herpesvirus infection, egress of nascent viral capsids from the nucleus is mediated by the viral nuclear egress complex (NEC). NEC deforms the inner nuclear membrane (INM) around the capsid by forming a hexagonal array. However, how the NEC coat interacts with the capsid and how curved coats are generated to enable budding is yet unclear. Here, by structure-guided truncations, confocal microscopy, and cryoelectron tomography, we show that binding of the capsid protein UL25 promotes the formation of NEC pentagons rather than hexagons. We hypothesize that during nuclear budding, binding of UL25 situated at the pentagonal capsid vertices to the NEC at the INM promotes formation of NEC pentagons that would anchor the NEC coat to the capsid. Incorporation of NEC pentagons at the points of contact with the vertices would also promote assembly of the curved hexagonal NEC coat around the capsid, leading to productive egress of UL25-decorated capsids.

Highlights

To replicate, all viruses must assemble their progeny virions and release them from the cell while overcoming many obstacles, including cellular compartmentalization
herpes simplex virus type 1 (HSV-1) UL25 can be expressed in soluble form in E. coli only when residues 1–44 are deleted (Bowman et al, 2006)
The intrinsic ability of the nuclear egress complex (NEC) to deform and bud membranes and to oligomerize into a hexagonal coat is well established. It is unclear how the capsid triggers the formation of the NEC coat around it or how the NEC coat is anchored to the capsid

Summary

Introduction

All viruses must assemble their progeny virions and release them from the cell while overcoming many obstacles, including cellular compartmentalization. The high-resolution crystal structure of the hexagonal NEC lattice revealed interactions at the lattice interfaces (Bigalke and Heldwein, 2015), and subsequent work confirmed that mutations that disrupt oligomeric interfaces reduce budding in vitro (Bigalke and Heldwein, 2015; Bigalke et al, 2014) and in vivo (Arii et al, 2019; Roller et al, 2010) These findings established the NEC as a viral budding machine that generates negative membrane curvature by oligomerizing into a hexagonal coat on the surface of the membrane. We hypothesize that during nuclear budding, NEC pentagons are formed at the points of contact with the capsid vertices and that they both help anchor the NEC coat to the capsid and generate appropriate coat curvature through the inclusion of pentagons into a hexagonal coat as it assembles around the capsid This mechanism would ensure successful budding and egress of the UL25-decorated viral capsid

Results

Discussion

Materials and methods

Funding Funder National Institutes of Health