HSV-1 Glycoproteins Are Delivered to Virus Assembly Sites Through Dynamin-Dependent Endocytosis.
HSV-1 glycoprotein endocytosis
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Albecka, A., Laine, R., Janssen, A., Kaminski, C., & Crump, C. (2015). HSV-1 Glycoproteins Are Delivered to Virus Assembly Sites Through Dynamin-Dependent Endocytosis.. Traffic, 17 (1), 21-39. https://doi.org/10.1111/tra.12340
Herpes simplex virus-1 (HSV-1) is a large enveloped DNA virus that belongs to the family of Herpesviridae. It has been recently shown that the cytoplasmic membranes that wrap the newly assembled capsids are endocytic compartments derived from the plasma membrane. Here, we show that dynamin-dependent endocytosis plays a major role in this process. Dominant-negative dynamin and clathrin adaptor AP180 significantly decrease virus production. Moreover, inhibitors targeting dynamin and clathrin lead to a decreased transport of glycoproteins to cytoplasmic capsids, confirming that glycoproteins are delivered to assembly sites via endocytosis. We also show that certain combinations of glycoproteins colocalize with each other and with the components of clathrin-dependent and -independent endocytosis pathways. Importantly, we demonstrate that the uptake of neutralizing antibodies that bind to glycoproteins when they become exposed on the cell surface during virus particle assembly leads to the production of non-infectious HSV-1. Our results demonstrate that transport of viral glycoproteins to the plasma membrane prior to endocytosis is the major route by which these proteins are localized to the cytoplasmic virus assembly compartments. This highlights the importance of endocytosis as a major protein-sorting event during HSV-1 envelopment.
HSV, dSTORM, dynamin, endocytosis, glycoprotein, virus assembly, Animals, COS Cells, Cercopithecus aethiops, Clathrin, Dynamins, Endocytosis, Glycoproteins, Herpesvirus 1, Human, Humans, Monomeric Clathrin Assembly Proteins, Protein Transport, Vero Cells, Viral Proteins, Virus Assembly
This work was supported by grants from the Leverhulme Trust (grant RPG‐2012‐793), the Royal Society (University Research Fellowship UF090010), the Engineering and Physical Sciences Research Council, UK (grant EP/H018301/1, EP/L015889/1) and by the Medical Research Council (grant MR/K015850/1).
Leverhulme Trust (RPG-2012-793)
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External DOI: https://doi.org/10.1111/tra.12340
This record's URL: https://www.repository.cam.ac.uk/handle/1810/251157
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/