Saiz-Ros, N. et al. (2019) Host vesicle fusion protein VAPB contributes to the nuclear egress stage of herpes simplex virus type-1 (HSV-1) replication. Cells, 8(2), 120. (doi: 10.3390/cells8020120)
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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.
| Item Type: | Articles |
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| Additional Information: | N.S.-R. was supported by a University of Edinburgh Principal’s studentship, C.R.D. was supported by Wellcome Trust studentship 109089, S.V.G., I.E., A.S. and L.D. were supported by the Medical Research Council and grant number PhD-772-2014 from Medical Research Scotland. S.V. and M.M. were supported by the Medical Research Council. S.K.S and L.F. are supported by the Stowers Institute for Medical Research. This work was supported by Wellcome Senior Research Fellowship 095209 to E.C.S. and the Wellcome Centre for Cell Biology core grant 092076. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Graham, Professor Sheila and Dong, Li and Stevenson, Mr Andrew and McElwee, Dr Marion and Epifano, Dr Ilaria and Vijayakrishnan, Dr Swetha |
| Authors: | 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., and Schirmer, E. C. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Journal Name: | Cells |
| Publisher: | MDPI |
| ISSN: | 2073-4409 |
| ISSN (Online): | 2073-4409 |
| Copyright Holders: | Copyright © 2019 The Authors |
| First Published: | First published in Cells 8(2):120 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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