ABSTRACT
Upon entry, neuroinvasive herpesviruses traffic from axon terminals to the nuclei of neurons resident in peripheral ganglia, where the viral DNA is deposited. A detailed analysis of herpes simplex virus type 1 (HSV-1) transport dynamics in axons following entry is currently lacking. Here, time lapse fluorescence microscopy was used to compare the postentry viral transport of two neurotropic herpesviruses: HSV-1 and pseudorabies virus (PRV). HSV-1 capsid transport dynamics were indistinguishable from those of PRV and did not differ in neurons of human, mouse, or avian origin. Simultaneous tracking of capsids and tegument proteins demonstrated that the composition of actively transporting HSV-1 is remarkably similar to that of PRV. This quantitative assessment of HSV-1 axon transport following entry demonstrates that HSV-1 and PRV share a conserved mechanism for postentry retrograde transport in axons and provides the foundation for further studies of the retrograde transport process.
Subject(s)
Axons , Herpesvirus 1, Human/physiology , Herpesvirus 1, Suid/physiology , Animals , Base Sequence , Cells, Cultured , Chick Embryo , DNA Primers , Humans , Mice , Microscopy, Fluorescence , Neurons/virologyABSTRACT
The capsids of neurotropic herpesviruses have the remarkable ability to move in specific directions within axons. By modulating bidirectional capsid transport to favor either retrograde (minus-end) or anterograde (plus-end) motion, these viruses travel to sensory ganglia or peripheral tissue at specific stages of infection. By using correlative motion analysis to simultaneously monitor the trafficking of distinct viral proteins in living neurons, we demonstrate that viral "tegument" proteins are complexed to capsids moving in axons. The removal of a subset of tegument proteins from capsids invariably preceded retrograde transport to the cell body in sensory ganglia, whereas addition of these proteins was coupled to anterograde transport of progeny capsids to the distal axon. Although capsid transport never occurred without associated tegument proteins, anterograde-specific tegument proteins were competent to travel to the distal axon independent of capsids. These findings are compatible with a model of viral bidirectional transport in which tegument proteins direct capsid traffic to specific intracellular locations during the infectious cycle.
