Abstract
All viruses produce infectious particles that possess some degree of stability in the extracellular environment yet disassemble upon cell contact and entry. For the alphaherpesviruses, which include many neuroinvasive viruses of mammals, these metastable virions consist of an icosahedral capsid surrounded by a protein matrix (referred to as the tegument) and a lipid envelope studded with glycoproteins. Whereas the capsid of these viruses is a rigid structure encasing the DNA genome, the tegument and envelope are dynamic assemblies that orchestrate a sequential series of events that ends with the delivery of the genome into the nucleus. These particles are adapted to infect two different polarized cell types in their hosts: epithelial cells and neurons of the peripheral nervous system. This review considers how the virion is assembled into a primed state and is targeted to infect these cell types such that the incoming particles can subsequently negotiate the diverse environments they encounter on their way from plasma membrane to nucleus and thereby achieve their remarkably robust neuroinvasive infectious cycle.