Local modulation of plus-end transport targets herpesvirus entry and egress in sensory axons

Abstract

The core structures of many viruses move within cells by association with host cytoskeletal motor proteins; however, the mechanisms by which intracellular viral particles are transported toward sites of replication or the cell periphery at distinct stages of infection remain to be understood. The regulation of herpesvirus directional transport in sensory neurons was examined by tracking individual viral capsids within axons at multiple frames per s. After entry into axons, capsids underwent bidirectional and saltatory movement to the cell body independently of endosomes. A comparison of entry transport to a previous analysis of capsid axonal transport during egress revealed that capsid targeting in and out of cells occurs by modulation of plus-end, but not minus-end, motion. Entry transport was unperturbed by the presence of egressing virus from a prior infection, indicating that transport direction is not modulated globally by viral gene expression, but rather directly by a component of the viral particle.virus ͉ neuron

Transport and egress of herpes simplex virus in neurons

“…For egress, retrograde transport was the same speed as entry (suggesting the same motor was recruited, i.e. dynein) while anterograde transport was now faster resulting in nett move-HSV transport and egress HSV transport and egress 45 45 Copyright [105,129]. It was concluded that the activity of the anterograde motor (assuming the same kinesin was recruited during entry and egress) is directly regulated by the viral cargo [129] as has been suggested for cellular cargo [130].…”

“…Direct interaction of DYNC1I and KLC also implies that kinesin bound to cargo can recruit and coordinate the activity of dynein and vice versa [128]. Measurements in real-time of GFP-pUL35-labelled PrV in chick DRGs indicates that herpesvirus capsid transport during entry and egress, at least within axons, is also bi-directional [105,129]. For PrV entry, movement was observed in both directions but the speed of retrograde transport was greater than anterograde transport resulting in net movement up the axon [129].…”

“…Measurements in real-time of GFP-pUL35-labelled PrV in chick DRGs indicates that herpesvirus capsid transport during entry and egress, at least within axons, is also bi-directional [105,129]. For PrV entry, movement was observed in both directions but the speed of retrograde transport was greater than anterograde transport resulting in net movement up the axon [129]. For egress, retrograde transport was the same speed as entry (suggesting the same motor was recruited, i.e.…”

“…dynein) while anterograde transport was now faster resulting in nett move-HSV transport and egress HSV transport and egress 45 45 Copyright [105,129]. It was concluded that the activity of the anterograde motor (assuming the same kinesin was recruited during entry and egress) is directly regulated by the viral cargo [129] as has been suggested for cellular cargo [130]. Alternatively, if the viral capsid/tegument structure does vary in composition during entry and egress, as appears to be the case for HSV-1 and PrV, then different kinesins, with different rates of transport, may be recruited during entry and egress.…”

On the use of in vivo cargo velocity as a biophysical marker

“…Much of this transport is bi-directional [5,6], including mRNA particles [7], mitochondria [2,8], virus particles [9,10], neuronal vesicles [11], etc. Typically, travel in a given direction (a "run") is short (1-2 μm) [1] though longer runs (~10 μm) are observed in some systems [10,12,13]. This observation is surprising since in vitro work suggests that when cargos are moved by multiple motors, they have very long run lengths [6,14,15].…”