MOLECULAR MECHANISMS OF NEUROTROPIC HERPESVIRUS INVASION AND SPREAD IN THE CNS

Pseudorabies virus (PRV) is a herpesvirus in the subfamily alphaherpes virinae (the alpha herpesviruses). After primary infection at mucosal surfaces, PRV infects the peripheral nervous system in its natural hos t (swine) with occasional invasion of the central nervous system. When other hosts (including cows and rodents) are infected, the infection almost always gives rise to fatal disease in the CNS as a result of in fection of peripheral neurons and subsequent spread to the brain. Part of the ability to cause fatal CNS disease can be attributed to a vira l glycoprotein called gE. Viruses lacking gE are thought to be less vi rulent because they do not spread efficiently from cell to cell. Based on a set of gE mutations we have constructed, we suggest that these t wo phenotypes of cell-cell spread and virulence reflect separate funct ions of the gE protein. In this report, we show that viruses carrying these new gE mutations have marked reduction in virulence, yet spread efficiently in defined neural circuits in the rat brain. As such, they offer new insight and opportunities for understanding of viral diseas e and host response to injury, as well as in the construction of viral tracers of neuronal connections. (C) 1998 Elsevier Science Ltd. All r ights reserved.