title: Analysis of Rab GTPase-activating proteins indicates that Rab1a/b and Rab43 are important for herpes simplex virus 1 secondary envelopment.
abstract: Assembly of herpes simplex virus 1 (HSV-1) occurs in the cytoplasm, where the capsid and tegument bud into host cell membranes. It is at this point that the viral glycoproteins are incorporated into the virion, as they are located at the assembly site. We investigated the role of the Rab GTPases in coordinating the assembly process by overexpressing 37 human Rab GTPase-activating proteins (GAPs) and assessing infectious titers. Rab GTPases are key cellular regulators of membrane trafficking events that, by their membrane association and binding of effector proteins, ensure the appropriate fusion of membranes. We identified that TBC1D20 and RN-tre and their partner Rabs, Rab1a/b and Rab43, respectively, are important for virion assembly. In the absence of Rab1a/b, the viral glycoproteins are unable to traffic from the endoplasmic reticulum to the assembly compartment, and thus unenveloped particles build up in the cytoplasm. The defect resulting from Rab43 depletion is somewhat more complex, but it appears that the fragmentation and dispersal of the trans-Golgi network and associated membranes render these compartments unable to support secondary envelopment.
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
authors.forename: Helen L
authors.initials: HL
authors.lastname: Zenner
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Yoshimura
authors.forename: Francis A
authors.initials: FA
authors.lastname: Barr
authors.forename: Colin M
authors.initials: CM
authors.lastname: Crump
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism / Q000821:virology; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000821:virology; D005455:Fluorescent Antibody Technique; D020690:GTPase-Activating Proteins / Q000378:metabolism; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008854:Microscopy, Electron; D034622:RNA Interference; D034741:RNA, Small Interfering; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000378:metabolism*; D019065:Virus Assembly; D014779:Virus Replication; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020761:rab1 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D020690:GTPase-Activating Proteins; D034741:RNA, Small Interfering; D014759:Viral Envelope Proteins; D020691:rab GTP-Binding Proteins; D020761:rab1 GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C526344:TBC1D20 protein, human; C100665:USP6NL protein, human; C529587:Rab1B protein, human