Inner tegument proteins of Herpes Simplex Virus are sufficient for intracellular capsid motility in neurons but not for axonal targeting
| العنوان: | Inner tegument proteins of Herpes Simplex Virus are sufficient for intracellular capsid motility in neurons but not for axonal targeting |
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| المؤلفون: | Dagmara Bialy, Martin Koltzenburg, Oliver Müller, Beate Sodeik, Katinka Döhner, Jens B. Bosse, Bodo Rosenhahn, Maike Hegemann, Anne Binz, Rudolf Bauerfeind, Claus-Henning Nagel, Lyudmila Ivanova, Anja Pohlmann, Anna Buch, Abel Viejo-Borbolla |
| المصدر: | PLoS Pathogens 13 (2017), Nr. 12 PLoS Pathogens PLoS Pathogens, Vol 13, Iss 12, p e1006813 (2017) |
| بيانات النشر: | San Francisco, CA : Public Library of Science (PLoS), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, UL20 protein, Herpes simplex virus type 1, viruses, Herpesvirus 1, Human, medicine.disease_cause, Microtubules, Axonal Transport, Viral Packaging, Virions, Vero cell line, Mice, Nerve Fibers, Tegument Proteins, Animal Cells, Ganglia, Spinal, Chlorocebus aethiops, pathogenicity, animal, genetics, Biology (General), Axon, Cytoskeleton, Cells, Cultured, axon, Human alphaherpesvirus 1, Neurons, movement (physiology), ultrastructure, Cell biology, virology, virus capsid, medicine.anatomical_structure, Capsid, Cell Processes, Host-Pathogen Interactions, UL36 protein, Human herpesvirus 1, Cellular Types, Cellular Structures and Organelles, nerve cell, Research Article, viral protein, QH301-705.5, Viral protein, Movement, Immunology, Viral Structure, Biology, Microbiology, Cercopithecus aethiops, 03 medical and health sciences, Viral Proteins, Microscopy, Electron, Transmission, Microtubule, Virology, transmission electron microscopy, Genetics, medicine, Animals, Humans, Vesicles, ddc:610, human, Molecular Biology, host pathogen interaction, Vero Cells, mouse, Viral Structural Proteins, cell culture, Biology and Life Sciences, Herpes Simplex, Cell Biology, RC581-607, biochemical phenomena, metabolism, and nutrition, UL37 protein, Human herpesvirus 1, spinal ganglion, Viral Replication, Axons, 030104 developmental biology, Herpes simplex virus, nervous system, Cytoplasm, nerve fiber transport, Cellular Neuroscience, physiology, Mutation, Axoplasmic transport, Parasitology, Soma, Dewey Decimal Classification::600 | Technik::610 | Medizin, Gesundheit, Immunologic diseases. Allergy, Neuroscience |
| الوصف: | 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. Author summary Human and animal alphaherpesviruses establish lifelong latent infections in neurons of the peripheral nervous system and cause many diseases upon primary infection as well as following reactivation from latency. The highly prevalent human herpes simplex viruses HSV-1 and HSV-2 are responsible for facial and genital herpes, potentially blinding eye infections, and life-threatening encephalitis and meningitis. Here, we asked how these viruses master the bottleneck of being targeted from the neuronal somata to the axons. Our data suggest that only transport vesicles harboring fully matured virus particles can enter axons for spreading infection to the brain or the peripheral organs. Our data imply that the limiting membrane of the transport vesicles must expose viral or host receptors to recruit the microtubule motors required for axonal transport. Inhibiting such viral factors on the surface of the transport vesicles might provide novel therapeutic approaches to prevent the spread of alphaherpesviruses in the nervous system. |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::45cf400437d9a14cd559fb40d7ed689bTest https://www.repo.uni-hannover.de/handle/123456789/5395Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....45cf400437d9a14cd559fb40d7ed689b |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |