title: Rab6 dependent post-Golgi trafficking of HSV1 envelope proteins to sites of virus envelopment.
abstract: Herpes simplex virus 1 (HSV1) is an enveloped virus that uses undefined transport carriers for trafficking of its glycoproteins to envelopment sites. Screening of an siRNA library against 60 Rab GTPases revealed Rab6 as the principal Rab involved in HSV1 infection, with its depletion preventing Golgi-to-plasma membrane transport of HSV1 glycoproteins in a pathway used by several integral membrane proteins but not the luminal secreted protein Gaussia luciferase. Knockdown of Rab6 reduced virus yield to 1% and inhibited capsid envelopment, revealing glycoprotein exocytosis as a prerequisite for morphogenesis. Rab6-dependent virus production did not require the effectors myosin-II, bicaudal-D, dynactin-1 or rabkinesin-6, but was facilitated by ERC1, a factor involved in linking microtubules to the cell cortex. Tubulation and exocytosis of Rab6-positive, glycoprotein-containing membranes from the Golgi was substantially augmented by infection, resulting in enhanced and targeted delivery to cell tips. This reveals HSV1 morphogenesis as one of the first biological processes shown to be dependent on the exocytic activity of Rab6.
authors.affiliation: Section of Virology, Faculty of Medicine, Imperial College London, London, W2 1PG, UK.
authors.forename: Helen L
authors.initials: HL
authors.lastname: Johns
authors.forename: Claudia
authors.initials: C
authors.lastname: Gonzalez-Lopez
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Sayers
authors.forename: Michael
authors.initials: M
authors.lastname: Hollinshead
authors.forename: Gillian
authors.initials: G
authors.lastname: Elliott
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D005089:Exocytosis; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D014759:Viral Envelope Proteins / Q000378:metabolism*; D019065:Virus Assembly; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D021601:trans-Golgi Network / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C468925:ERC1 protein, human; D009419:Nerve Tissue Proteins; C094135:Rab6 protein; D014759:Viral Envelope Proteins; D020691:rab GTP-Binding Proteins
keywords: Gaussia luciferase; Rab6; Rab6 effector; VSV-G; herpes simplex virus; post-Golgi carrier; secretion