Chapter 20 - Molecular Properties of Alphaherpesviruses Used in Transneuronal Pathway Tracing

Abstract

This chapter focuses on the molecular properties of the alphaherpesviruses in initiation and spread of infection in cell culture and the role played by viral glycoproteins in these processes. It also discusses the role of other viral gene products in neurotropism of alphaherpesviruses in vivo and the importance of the results derived from cultured continuous cell lines, with regard to the situation in infection of the nervous system in the animal host. Several group of viruses exhibit a distinct tropism for the central nervous system of their host species, for example, the poliovirus, the rhabdoviruses, and the herpes virus. After peripheral infection these viruses enter neurons and spread within the CNS until they reach terminal target cells whose destruction ultimately leads to severe disease or death. There are four viruses, belonging to two different virus families, that are most prominent in transneuronal pathway tracing: The rhabdoviruses vesicular stomatitis virus (VSV) and rabies virus, and the alphaherpesviruses herpes simplex virus type 1 (HSV-1) and suid herpes virus 1, also called pseudorabies virus. Penetration between virion envelope and cellular cytoplasmic membrane requires a number of herpes virus glycoprotein–cell surface receptor interactions with several virion glycoproteins acting simultaneously or in a cascade-like fashion. The spread of infection within cell culture and the infected host can occur by two mechanisms: release of free infectious virions from infected cells that initiate a novel round of infection from outside and direct virus transfer from primary infected to adjacent noninfected cells. The chapter details the replicative cycle of the herpes viruses, initiation of infection by aplphaherpesviruses including attachment and penetration, viral spread by direct cell-to-cell transmission, infection of neurons, transneuronal transfer, molecular analysis on PrV strain Bartha, other proteins influencing neurotropism and neurovirulence of alpha herpesviruses, and reporter genes.