Pseudorabies Virus Replication and Assembly in the Rodent Central Nervous System

The chapter identifies the viral gene products responsible for the selective tropism of PRV mutants and determines if the inability of these strains to invade functionally distinct components of the visual neuraxis was a property of the virus or the host neurons.

Abstract

This chapter focuses on the swine alphaherpesvirus known as pseudorabies, general principals derived from studies of herpes simplex virus (HSV), the use of alphaherpesviruses for gene delivery, and other alphaherpesviruses. It begins with discussing the virion replication and assembly in neurons including the detailed virion structure, DNA replication and packaging, capsid envelopment, intracellular transport of virions, and the role of viral envelope glycoproteins in viral assembly and transport. Alphaherpesviruses invade the nervous system and replicate within synaptically linked populations of neurons. The tropism and invasive characteristics of HSV and pseudorabies are employed for delivery of foreign genes to the nervous system as reporters for analysis of neural circuitry, therapeutic manipulation of neuronal function, or treatment of malignant brain tumors. The factors that are considered in evaluating the utility of using viruses for tract tracing or gene delivery are the route of inoculation, the invasive characteristics of the virus, the neurovirulence and cytopathic consequences of infection, and the cell-specific aspects of viral invasion and replication. . Differential sorting of alphaherpesvirus glycoproteins in polarized epithelial cells is also demonstrated and it's shown that glycoproteins of vesicular stomatitus virus are preferentially sorted into the somata and dendrites of cultured hippocampal neurons. The extent of viral transport through the CNS is also dependent upon the distribution of newly replicated virions within an infected cell. The chapter identifies the viral gene products responsible for the selective tropism of PRV mutants and determines if the inability of these strains to invade functionally distinct components of the visual neuraxis was a property of the virus or the host neurons. It also details the role of glia in dissemination of viral infection, which includes determining the susceptibility of different classes of glia to viral infection.