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.
Highlights
Intracellular trafficking between organelles is regulated by the Rab group of small GTPases [1]
Depletion of Rab6 GTPase inhibits Herpes simplex virus 1 (HSV1) virus production To investigate cellular transport pathways involved in HSV1 morphogenesis, we carried out a screen of human Rab GTPases using an siRNA library directed against the 60 Rabs in HeLa cells, a cell line commonly used for HSV1 infection
In light of our results showing failed glycoprotein trafficking to the plasma membrane (PM) in Rab6 depleted cells, we investigated the effect of Rab6 depletion on the trafficking of the tegument protein VP22, a protein that is known to be assembled into the virus by interacting with the cytoplasmic tails of the glycoproteins gE and gM [40]
Summary
Intracellular trafficking between organelles is regulated by the Rab group of small GTPases [1]. We suggest that virus envelope proteins are first transported through the Golgi/TGN to the PM ahead of capsid release from the nucleus, and are retrieved into the recycling endocytic pathway to provide the final wrapping membranes. We conclude that HSV1 activates a Rab6specific exocytic pathway to transport virus glycoproteins from the Golgi/TGN to the PM, and provide a membrane population that is subsequently used for virus wrapping by endocytic retrieval. This reveals that the Rab specific post-Golgi pathway is fundamental to HSV1 envelopment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
