Transport and egress of herpes simplex virus in neurons.
The mechanisms of axonal transport of the alphaherpesviruses, HSV and pseudorabies virus (PrV), in neuronal axons are of fundamental interest, particularly in comparison with other viruses, and offer potential sites for antiviral intervention or development of gene therapy vectors. These herpesviruses are transported rapidly along microtubules (MTs) in the retrograde direction from the axon terminus to the dorsal root ganglion and then anterogradely in the opposite direction. Retrograde transport follows fusion and deenvelopment of the viral capsid at the axonal membrane followed by loss of most of the tegument proteins and then binding of the capsid via one or more viral proteins (VPs) to the retrograde molecular motor dynein. The HSV capsid protein pUL35 has been shown to bind to the dynein light chain Tctex1 but is likely to be accompanied by additional dynein binding of an inner tegument protein. The mechanism of anterograde transport is much more controversial with different processes being claimed for PrV and HSV: separate transport of HSV capsid/tegument and glycoproteins versus PrV transport as an enveloped virion. The controversy has not been resolved despite application, in several laboratories, of confocal microscopy (CFM), real-time fluorescence with viruses dual labelled on capsid and glycoprotein, electron microscopy in situ and immuno-electron microscopy. Different processes for each virus seem counterintuitive although they are the most divergent in the alphaherpesvirus subfamily. Current hypotheses suggest that unenveloped HSV capsids complete assembly in the axonal growth cones and varicosities, whereas with PrV unenveloped capsids are only found travelling in a retrograde direction.
Diefenbach
Russell J
RJ
Centre for Virus Research, Westmead Millennium Institute, Westmead Hospital and the University of Sydney, Westmead, NSW 2145, Australia.
Miranda-Saksena
Monica
M
Douglas
Mark W
MW
Cunningham
Anthony L
AL
D000818:Animals; D001369:Axons / Q000821:virology; D001692:Biological Transport; D036022:Capsid Proteins / Q000378:metabolism; D004398:Dyneins / Q000378:metabolism; D005727:Ganglia, Spinal / Q000821:virology; D006561:Herpes Simplex / Q000821:virology*; D011558:Herpesvirus 1, Suid / Q000502:physiology; D006801:Humans; D016547:Kinesins / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000821:virology*; D009687:Nuclear Proteins / Q000378:metabolism; D021381:Protein Transport; D018139:Simplexvirus / Q000502:physiology*; D014779:Virus Replication; D056427:t-Complex Genome Region
D036022:Capsid Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D004398:Dyneins; D016547:Kinesins