Bovine Herpesvirus 1 Invasion of Sensory Neurons by Retrograde Axonal Transport Is Dependent on the pUL37 Region 2 Effector

Austin M. Stults, Patricia J. Sollars, Kelly D. Heath, Sarah J. Sillman, Gary E. Pickard, Gregory A. Smith

Research output: Contribution to journalArticlepeer-review

Abstract

Following exposure and replication at mucosal surfaces, most alphaherpesviruses invade the peripheral nervous system by retrograde axonal transport and establish lifelong latent infections in the peripheral ganglia. Reactivation of ganglionic infections is followed by anterograde axonal transport of virions back to body surfaces where viral replication results in disease that can range from moderate to severe in presentation. In the case of bovine herpesvirus 1 (BoHV-1), replication in the epithelial mucosa presents as infectious bovine rhinotracheitis (IBR), a respiratory disease of significant economic impact. In this study, we provide a live-cell analysis of BoHV-1 retrograde axonal transport relative to the model alphaherpesvirus pathogen pseudorabies virus (PRV) and demonstrate that this critical neuroinvasive step is conserved between the two viruses. In addition, we report that the BoHV-1 pUL37 tegument protein supports processive retrograde motion in infected axons and invasion of the calf peripheral nervous system. IMPORTANCE A molecular and cellular understanding of the retrograde axonal transport process that underlies the neuroinvasive properties of the alphaherpesviruses is established from studies of herpes simplex virus and pseudorabies virus. The degree to which this phenotype is conserved in other related viruses has largely not been examined. We provide a time-lapse analysis of the retrograde axonal transport kinetics of bovine herpesvirus 1 and demonstrate that mutation of the pUL37 region 2 effector affords a strategy to produce live-attenuated vaccines for enhanced protection of cattle.

Original languageEnglish (US)
JournalJournal of virology
Volume96
Issue number9
DOIs
StatePublished - May 2022

Keywords

  • BoHV-1
  • axonal transport
  • bovine
  • calf
  • herpesvirus
  • neuroinvasion
  • neuron
  • retrograde

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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