Skip to main content

Research Repository

Advanced Search

Host Vesicle Fusion Protein VAPB Contributes to the Nuclear Egress Stage of Herpes Simplex Virus Type-1 (HSV-1) Replication

Saiz-Ros, Natalia; Czapiewski, Rafal; Epifano, Ilaria; Stevenson, Andrew; Swanson, Selene; Dixon, Charles; Zamora, Dario; McElwee, Marion; Vijayakrishnan, Swetha; Richardson, Christine; Dong, Li; Kelly, David; Pytowski, Lior; Goldberg, Martin; Florens, Laurence; Graham, Sheila; Schirmer, Eric

Host Vesicle Fusion Protein VAPB Contributes to the Nuclear Egress Stage of Herpes Simplex Virus Type-1 (HSV-1) Replication Thumbnail


Authors

Natalia Saiz-Ros

Rafal Czapiewski

Ilaria Epifano

Andrew Stevenson

Selene Swanson

Charles Dixon

Dario Zamora

Marion McElwee

Swetha Vijayakrishnan

Christine Richardson

Li Dong

David Kelly

Lior Pytowski

Laurence Florens

Sheila Graham

Eric Schirmer



Abstract

The primary envelopment/de-envelopment of Herpes viruses during nuclear exit is poorly understood. In Herpes simplex virus type-1 (HSV-1), proteins pUL31 and pUL34 are critical, while pUS3 and some others contribute; however, efficient membrane fusion may require additional host proteins. We postulated that vesicle fusion proteins present in the nuclear envelope might facilitate primary envelopment and/or de-envelopment fusion with the outer nuclear membrane. Indeed, a subpopulation of vesicle-associated membrane protein-associated protein B (VAPB), a known vesicle trafficking protein, was present in the nuclear membrane co-locating with pUL34. VAPB knockdown significantly reduced both cell-associated and supernatant virus titers. Moreover, VAPB depletion reduced cytoplasmic accumulation of virus particles and increased levels of nuclear encapsidated viral DNA. These results suggest that VAPB is an important player in the exit of primary enveloped HSV-1 virions from the nucleus. Importantly, VAPB knockdown did not alter pUL34, calnexin or GM-130 localization during infection, arguing against an indirect effect of VAPB on cellular vesicles and trafficking. Immunogold-labelling electron microscopy confirmed VAPB presence in nuclear membranes and moreover associated with primary enveloped HSV-1 particles. These data suggest that VAPB could be a cellular component of a complex that facilitates UL31/UL34/US3-mediated HSV-1 nuclear egress.

Citation

Saiz-Ros, N., Czapiewski, R., Epifano, I., Stevenson, A., Swanson, S., Dixon, C., …Schirmer, E. (2019). Host Vesicle Fusion Protein VAPB Contributes to the Nuclear Egress Stage of Herpes Simplex Virus Type-1 (HSV-1) Replication. Cells, 8(2), Article 120. https://doi.org/10.3390/cells8020120

Journal Article Type Article
Acceptance Date Jan 31, 2019
Online Publication Date Feb 3, 2019
Publication Date Feb 3, 2019
Deposit Date Feb 11, 2019
Publicly Available Date Feb 15, 2019
Journal Cells
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 8
Issue 2
Article Number 120
DOI https://doi.org/10.3390/cells8020120

Files

Published Journal Article (13.5 Mb)
PDF

Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright Statement
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).







You might also like



Downloadable Citations