Dynamic ubiquitination drives herpesvirus neuroinvasion

Nicholas J. Huffmaster, Patricia J Sollars, Alexsia L. Richards, Gary E Pickard, Gregory A. Smith

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Neuroinvasive herpesviruses display a remarkable propensity to enter the nervous system of healthy individuals in the absence of obvious trauma at the site of inoculation. We document a repurposing of cellular ubiquitin during infection to switch the virus between two invasive states. The states act sequentially to defeat consecutive host barriers of the peripheral nervous system and together promote the potent neuroinvasive phenotype. The first state directs virus access to nerve endings in peripheral tissue, whereas the second delivers virus particles within nerve fibers to the neural ganglia. Mutant viruses locked in either state remain competent to overcome the corresponding barrier but fail to invade the nervous system. The herpesvirus "ubiquitin switch" may explain the unusual ability of these viruses to routinely enter the nervous system and, as a consequence, their prevalence in human and veterinary hosts.

Original languageEnglish (US)
Pages (from-to)12818-12823
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number41
DOIs
StatePublished - Oct 13 2015

Fingerprint

Herpesviridae
Ubiquitination
Nervous System
Viruses
Ubiquitin
Nerve Endings
Peripheral Nervous System
Nerve Fibers
Ganglia
Virion
Phenotype
Wounds and Injuries
Infection

Keywords

  • HSV-1
  • Herpesvirus
  • Neuroinvasion
  • PRV
  • Ubiquitin

ASJC Scopus subject areas

  • General

Cite this

Dynamic ubiquitination drives herpesvirus neuroinvasion. / Huffmaster, Nicholas J.; Sollars, Patricia J; Richards, Alexsia L.; Pickard, Gary E; Smith, Gregory A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 41, 13.10.2015, p. 12818-12823.

Research output: Contribution to journalArticle

Huffmaster, Nicholas J. ; Sollars, Patricia J ; Richards, Alexsia L. ; Pickard, Gary E ; Smith, Gregory A. / Dynamic ubiquitination drives herpesvirus neuroinvasion. In: Proceedings of the National Academy of Sciences of the United States of America. 2015 ; Vol. 112, No. 41. pp. 12818-12823.
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