Inner tegument proteins of Herpes Simplex Virus are sufficient for intracellular capsid motility in neurons but not for axonal targeting
Creators: name: Buch, Anna
name: Müller, Oliver
name: Ivanova, Lyudmila
name: Döhner, Katinka
name: Bialy, Dagmara
name: Bosse, Jens B.
name: Pohlmann, Anja
name: Binz, Anne
name: Hegemann, Maike
name: Nagel, Claus-Henning
name: Koltzenburg, Martin
name: Viejo-Borbolla, Abel
name: Rosenhahn, Bodo
name: Bauerfeind, Rudolf
name: Sodeik, Beate
Publisher: name: San Francisco, CA : Public Library of Science (PLoS)
Year: 2017
Subjects: subject: UL20 protein, Herpes simplex virus type 1
subject: UL36 protein, Human herpesvirus 1
subject: UL37 protein, Human herpesvirus 1
subject: viral protein
subject: animal
subject: axon
subject: cell culture
subject: Chlorocebus aethiops
subject: genetics
subject: herpes simplex
subject: host pathogen interaction
subject: human
subject: Human alphaherpesvirus 1
subject: mouse
subject: movement (physiology)
subject: mutation
subject: nerve cell
subject: nerve fiber transport
subject: pathogenicity
subject: physiology
subject: spinal ganglion
subject: transmission electron microscopy
subject: ultrastructure
subject: Vero cell line
subject: virology
subject: virus capsid
subject: Animals
subject: Axonal Transport
subject: Axons
subject: Capsid
subject: Cells, Cultured
subject: Cercopithecus aethiops
subject: Ganglia, Spinal
subject: Herpes Simplex
subject: Herpesvirus 1, Human
subject: Host-Pathogen Interactions
subject: Humans
subject: Mice
subject: Microscopy, Electron, Transmission
subject: Movement
subject: Mutation
subject: Neurons
subject: Vero Cells
subject: Viral Proteins
subject: Viral Structural Proteins
subject: Dewey Decimal Classification::600 | Technik::610 | Medizin, Gesundheit

description: Upon reactivation from latency and during lytic infections in neurons, alphaherpesviruses assemble cytosolic capsids, capsids associated with enveloping membranes, and transport vesicles harboring fully enveloped capsids. It is debated whether capsid envelopment of herpes simplex virus (HSV) is completed in the soma prior to axonal targeting or later, and whether the mechanisms are the same in neurons derived from embryos or from adult hosts. We used HSV mutants impaired in capsid envelopment to test whether the inner tegument proteins pUL36 or pUL37 necessary for microtubule-mediated capsid transport were sufficient for axonal capsid targeting in neurons derived from the dorsal root ganglia of adult mice. Such neurons were infected with HSV1-ΔUL20 whose capsids recruited pUL36 and pUL37, with HSV1-ΔUL37 whose capsids associate only with pUL36, or with HSV1-ΔUL36 that assembles capsids lacking both proteins. While capsids of HSV1-ΔUL20 were actively transported along microtubules in epithelial cells and in the somata of neurons, those of HSV1-ΔUL36 and -ΔUL37 could only diffuse in the cytoplasm. Employing a novel image analysis algorithm to quantify capsid targeting to axons, we show that only a few capsids of HSV1-ΔUL20 entered axons, while vesicles transporting gD utilized axonal transport efficiently and independently of pUL36, pUL37, or pUL20. Our data indicate that capsid motility in the somata of neurons mediated by pUL36 and pUL37 does not suffice for targeting capsids to axons, and suggest that capsid envelopment needs to be completed in the soma prior to targeting of herpes simplex virus to the axons, and to spreading from neurons to neighboring cells.