Inner tegument proteins of Herpes Simplex Virus are sufficient for intracellular capsid motility in neurons but not for axonal targeting

PLoS Pathogens
Anna BuchB Sodeik

Abstract

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 entere...Continue Reading

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Citations

Feb 24, 2018·Viruses·Monica Miranda-SaksenaAnthony L Cunningham
Feb 14, 2018·Viruses·Christopher E DenesRussell J Diefenbach
Mar 3, 2019·International Journal of Molecular Sciences·Sarah SchwarzAnnika Lehmbecker
Aug 27, 2019·Frontiers in Cell and Developmental Biology·Elaine L Bearer, Chengbiao Wu
Feb 23, 2020·Journal of Virology·Hao HuangLynn W Enquist
Aug 23, 2020·International Journal of Molecular Sciences·Imran Ahmad, Duncan W Wilson
Jan 22, 2021·Journal of Virology·Farhana MusarratKonstantin G Kousoulas
Apr 10, 2021·Virology·Grayson DuRaine, David C Johnson
Sep 1, 2021·Current Opinion in Virology·Katinka DöhnerBeate Sodeik

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Methods Mentioned

BETA
electron microscopy
fluorescence microscopy
confocal microscopy
transfection
PCR

Software Mentioned

ImageJ
Image J
MOSAIC
Adobe Photoshop
LSM
Prism

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