Journal Article

Endocytic tubules regulated by Rab GTPases 5 and 11 are used for envelopment of herpes simplex virus

Gonzalez‐Lopez, Claudia, Hollinshead, Michael, Sayers, Charlotte L, Johns, Helen L, Elliott, Gillian, Smith, Geoffrey L

2012

Overview

Enveloped viruses employ diverse and complex strategies for wrapping at cellular membranes, many of which are poorly understood. Here, an ultrastructural study of herpes simplex virus 1 (HSV1)‐infected cells revealed envelopment in tubular membranes. These tubules were labelled by the fluid phase marker horseradish peroxidase (HRP), and were observed to wrap capsids as early as 2 min after HRP addition, indicating that the envelope had recently cycled from the cell surface. Consistent with this, capsids did not colocalise with either the trans‐Golgi network marker TGN46 or late endosomal markers, but showed coincidence with the transferrin receptor. Virus glycoproteins were retrieved from the plasma membrane (PM) to label wrapping capsids, a process that was dependent on both dynamin and Rab5. Combined depletion of Rab5 and Rab11 reduced virus yield to <1%, resulting in aberrant localisation of capsids. These results suggest that endocytosis from the PM into endocytic tubules provides the main source of membrane for HSV1, and reveal a new mechanism for virus exploitation of the endocytic pathway. HSV capsids are enveloped by tubular membranes of early/recycling endosomal origin under the control of Rab5 and Rab11, rather than membranes derived from the trans‐Golgi network.

• Publisher: John Wiley & Sons, Ltd,Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
• Subject: Animals / Blotting, Western / Capsid - metabolism / Cell Membrane - metabolism / Cells, Cultured / Chlorocebus aethiops / EMBO20 / EMBO23 / Endocytosis / Endocytosis - physiology / Enzymes / Exploitation / Fibroblasts - cytology / Fibroblasts - metabolism / Fibroblasts - virology / Flow Cytometry / Fluorescent Antibody Technique / Glycoproteins / Glycoproteins - metabolism / HeLa Cells / Herpes Simplex - metabolism / Herpes Simplex - virology / Herpes simplex virus 1 / Herpes viruses / Herpesvirus 1, Human - metabolism / Horseradish Peroxidase - metabolism / HSV1 / Humans / Intracellular Membranes - metabolism / Lysosomal Membrane Proteins - metabolism / Membranes / Molecular biology / rab GTP-Binding Proteins - genetics / rab GTP-Binding Proteins - metabolism / Rab11 / Rab5 / rab5 GTP-Binding Proteins - genetics / rab5 GTP-Binding Proteins - metabolism / trans-Golgi network / trans-Golgi Network - metabolism / trans-Golgi Network - virology / Vero Cells / Viral Envelope Proteins - metabolism / Virus Assembly - physiology