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Open AccessArticle

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

1
The Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, UK
2
MRC-University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1QH, UK
3
Stowers Institute for Medical Research, Kansas City, MO 64110, USA
4
School of Biological and Biomedical Sciences, Durham University, Durham DH1 3LE, UK
*
Authors to whom correspondence should be addressed.
Cells 2019, 8(2), 120; https://doi.org/10.3390/cells8020120
Received: 22 October 2018 / Revised: 28 January 2019 / Accepted: 31 January 2019 / Published: 3 February 2019
(This article belongs to the Collection Lamins and Laminopathies)
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. View Full-Text
Keywords: nuclear envelope; nuclear membrane protein; herpes simplex virus-1 (HSV-1); vesicle fusion protein (VFP); VAPB; nuclear egress nuclear envelope; nuclear membrane protein; herpes simplex virus-1 (HSV-1); vesicle fusion protein (VFP); VAPB; nuclear egress
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Saiz-Ros, N.; Czapiewski, R.; Epifano, I.; Stevenson, A.; Swanson, S.K.; Dixon, C.R.; Zamora, D.B.; McElwee, M.; Vijayakrishnan, S.; Richardson, C.A.; Dong, L.; Kelly, D.A.; Pytowski, L.; Goldberg, M.W.; Florens, L.; Graham, S.V.; Schirmer, E.C. Host Vesicle Fusion Protein VAPB Contributes to the Nuclear Egress Stage of Herpes Simplex Virus Type-1 (HSV-1) Replication. Cells 2019, 8, 120.

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