The pUL37 tegument protein guides alpha-herpesvirus retrograde axonal transport to promote neuroinvasion

• DOI: 10.1371/journal.ppat.1006741
• Publication Date: 2017-12-07T18:51:29Z
• Authors: Alexsia L. Richards; Patricia J. Sollars; Jared D. Pitts; Austin M. Stults; Ekaterina E. Held...; Gary E. Pickard; Gregory A. Smith
• Keywords: Axoplasmic transport; Pseudorabies; Viral tegument; Neurotropic virus; Virus latency; Peripheral Nervous System; Enteric Nervous System

A hallmark property of the neurotropic alpha-herpesvirinae is dissemination infection to sensory and autonomic ganglia peripheral nervous system following an initial exposure at mucosal surfaces. The serve as latent virus reservoir source recurrent infections such cold sores (herpes simplex type I) shingles (varicella zoster virus). However, means by which these viruses routinely invade not fully understood. We report that internal virion component, pUL37 tegument protein, has a surface region essential neuroinvasion effector. Mutation this rendered herpes 1 (HSV-1) pseudorabies (PRV) incapable spreading retrograde axonal transport both in culture animals. By monitoring individual viral particles time-lapse fluorescence microscopy, mutant were determined lack characteristic sustained intracellular capsid motion along microtubules normally traffics capsids neural soma. Consistent with deficit, did reach sites latency ganglia, avirulent. Despite this, propagation tissues cultured epithelial cell lines remained robust. Selective elimination delivery long been sought after develop vaccines against ubiquitous, sometimes devastating viruses. In support potential, we find HSV-1 PRV mutated effector evoked effective vaccination subsequent challenges encephalitic disease. These findings demonstrate herpesviruses occurs virus-directed mechanism operates coordinating opposing microtubule motors favor ganglia. ability selectively eliminate from will be useful trans-synaptic mapping studies mammalian system, affords new paradigm for human veterinary herpesviruses.