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

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
• Public URL: https://durham-repository.worktribe.com/output/1308291