Abstract

Transneuronal transport of pseudorabies virus (PRV) from the retina to visual centers that mediate visual discrimination and reflexes requires specific genes in the unique short region of the PRV genome. In contrast, these same viral genes are not required to infect retinorecipient areas of the brain involved in circadian rhythm regulation. In this report, we demonstrate that viral mutants carrying defined deletions of the genes encoding glycoprotein gI or gp63, or both, result in the same dramatic transport defect. Efficient export of either gI or gp63 from the endoplasmic reticulum to the Golgi apparatus in a fibroblast cell line requires the presence of both proteins. We also show that gI and gp63 physically interact, as demonstrated by pulse-chase and sucrose gradient sedimentation experiments. Complex formation is rapid compared with homodimerization of PRV glycoprotein gIl. We suggest that gI and gp63 function in concert to affect neurotropism in the rat visual circuitry and that a heterodimer is likely to be the unit of function. Pseudorabies virus (PRV) is an alphaherpesvirus that causes economically significant disease in swine (2, 32, 33, 35, 45). PRV has a predilection to infect neurons, particu-larly sensory neurons, which often results in the establish-ment of latency in these neurons. Infection of the central nervous system (CNS) generally results in a lytic or produc-tive infection. It is clear from analyses in rodent models that invasion of the CNS from the periphery by PRV occurs in an ordered fashion in which the virus is contained within