Herpes simplex virus type 1 accumulation, envelopment, and exit in growth cones and varicosities in mid-distal regions of axons
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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.
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Different mechanisms of direct cell-to-cell spread have been documented including cell-cell fusion, synapse formation, or tunneling nanotubes.
“To achieve this goal, different mechanisms of direct cell-to-cell spread have been documented including cell-cell fusion, synapse formation, or tunneling nanotubes (Gerna et al., 2000; Jansens et al., 2017; Saksena et al., 2006).”
From Equid Herpesvirus-1 Exploits the Extracellular Matrix of Mononuclear Cells to Ensure Transport to Target Cells (2020) · cites this paper as Saksena et al., 2006
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- Authors
- Saksena, M. M., Wakisaka, H., Tijono, B., Boadle, R. A., Rixon, F., Takahashi, H., & Cunningham, A. L.
- Affiliations
- The University of Sydney (AU)
- Westmead Hospital (AU)
- MRC Virology unit, Institute of Virology, Church Street, Glasgow G11 5JR, United Kingdom
- Corresponding author
- Cunningham, Anthony L.
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2006-04
- Volume
- 80
- Issue
- 7
- Pages
- 3592-3606
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC1440394
- OpenAlex
- W2009214602
- Cited by
- 89
- References
- 53
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 6 · 2019: 3 · 2018: 3 · 2015: 7 · 2014: 5 · 2013: 4 · 2012: 9
- FWCI
- 7.35
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Virology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- Funders
- Westmead Millennium Institute for Medical Research
- Medical Research Council
- National Health and Medical Research Council (253617)
- Topics
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- herpes simplex virus type 1, anterograde axonal transport, alphaherpesvirus, viral envelopment, axonal varicosities, growth cones, viral egress, tegument proteins, envelope glycoprotein, exocytosis, dorsal root ganglia, axon ultrastructure
- MeSH terms
- Axons, Axonal Transport, Capsid, Ganglia, Spinal, Humans, Immunohistochemistry, Kinetics, Microscopy, Electron, Models, Biological, Organ Culture Techniques, Viral Envelope Proteins, Virion, Viral Structural Proteins, Herpesvirus 1, Human, Microscopy, Confocal, Growth Cones, Green Fluorescent Proteins
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