Transport and egress of herpes simplex virus in neurons

Abstract

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), realtime fluorescence with viruses dual labelled on capsid and glycoprotein, electron microscopy in situ and immunoelectron 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.

The Basic Domain of Herpes Simplex Virus 1 pUS9 Recruits Kinesin-1 To Facilitate Egress from Neurons

“…Our current findings with the three-chamber system using an HSV-1 pUS9 basic domain mutant also are similar to our observations with a complete deletion of pUS9 (53). A role for HSV-1 gE/gI extracellular domains in contributing to both anterograde axonal transport and possibly also in the spread from distal axons to nonneuronal cells has been reported recently (14) and adds further support to the notion of redundancy in transport processes essential for viral replication (49).…”

Level of Herpes Simplex Virus Type 1 Latency Correlates with Severity of Corneal Scarring and Exhaustion of CD8+T Cells in Trigeminal Ganglia of Latently Infected Mice

“…The latent virus can be reactivated spontaneously and return to the eye by traveling on the microtubules in an anterograde direction (18). The vast majority of primary HSV infections are either asymptomatic or so mildly symptomatic as to go almost completely unrecognized (11,14,20,61).…”

Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management

“…After primary infection of the mucosal or skin epithelium, the virus infects sensory neurons via interactions with cell-surface glycosaminoglycans such as heparan sulfate [7], and cell adhesion molecules such as nectin-1 [8,9], and travels to the neuronal cell body in the dorsal root ganglion via fast retrograde axonal transport [10,11].…”