Herpes simplex virus type 1 accumulation, envelopment, and exit in growth cones and varicosities in mid-distal regions of axons

Saksena, M.M., Wakisaka, H., Tijono, B., Boadle, R.A., Rixon, F., Takahashi, H. and Cunningham, A.L. (2006) Herpes simplex virus type 1 accumulation, envelopment, and exit in growth cones and varicosities in mid-distal regions of axons. Journal of Virology, 80(7), pp. 3592-3606. (doi: 10.1128/​JVI.80.7.3592-3606.2006) (PMID:16537627) (PMCID:PMC1440394)

[img] Text
3612.pdf

1MB

Abstract

The mechanism of anterograde transport of alphaherpesviruses in axons remains controversial. This study examined the transport, assembly, and egress of herpes simplex virus type 1 (HSV-1) in mid- and distal axons of infected explanted human fetal dorsal root ganglia using confocal microscopy and transmission electron microscopy (TEM) at 19, 24, and 48 h postinfection (p.i.). Confocal-microscopy studies showed that although capsid (VP5) and tegument (UL37) proteins were not uniformly present in axons until 24 h p.i., they colocalized with envelope (gG) proteins in axonal varicosities and in growth cones at 24 and 48 h p.i. TEM of longitudinal sections of axons in situ showed enveloped and unenveloped capsids in the axonal varicosities and growth cones, whereas in the midregion of the axons, predominantly unenveloped capsids were observed. Partially enveloped capsids, apparently budding into vesicles, were observed in axonal varicosities and growth cones, but not during viral attachment and entry into axons. Tegument proteins (VP22) were found associated with vesicles in growth cones, either alone or together with envelope (gD) proteins, by transmission immunoelectron microscopy. Extracellular virions were observed adjacent to axonal varicosities and growth cones, with some virions observed in crescent-shaped invaginations of the axonal plasma membrane, suggesting exit at these sites. These findings suggest that varicosities and growth cones are probable sites of HSV-1 envelopment of at least a proportion of virions in the mid- to distal axon. Envelopment probably occurs by budding of capsids into vesicles with associated tegument and envelope proteins. Virions appear to exit from these sites by exocytosis.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Rixon, Dr Frazer
Authors: Saksena, M.M., Wakisaka, H., Tijono, B., Boadle, R.A., Rixon, F., Takahashi, H., and Cunningham, A.L.
Subjects:Q Science > QR Microbiology > QR180 Immunology
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Journal of Virology
Journal Abbr.:J. Virol.
ISSN:0022-538X
ISSN (Online):1098-5514

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656531Structural studies on human virusesFrazer RixonMedical Research Council (MRC)MC_UU_12014/6MVLS III - CENTRE FOR VIRUS RESEARCH