LONG-TERM HERPES-SIMPLEX VIRUS TYPE-1 INFECTION OF NERVE GROWTH FACTOR-TREATED PC12 CELLS

The behaviour of herpes simplex virus type 1 (HSV-1) strain 17 in tiss ue cultures of PC12 cells treated with nerve growth factor (NGF) was s tudied. PC12 cells respond to NGF by ceasing to proliferate and extend ing long neurites. After differentiation with NGF, cultures were infec ted with HSV-1 and maintained in the presence of the hormone for sever al weeks. These longterm infected cultures were tested for HSV DNA, tr anscripts and the ability to produce virus, before and after NGF remov al. Before NGF removal, the cultures were characterized by little or n o virus production and the presence of HSV-1 DNA in a predominantly en dless form. In situ analysis of long-term infected cultures revealed l atency-associated transcript expression in only a portion of the cells . However, as shown by an infectious centre assay, virus was present i n almost all cells in the population. Moreover, removal of NGF from lo ng-term cultures resulted in the appearance of significantly increased amounts of virus in the media. The degree to which this system resemb les HSV latency in vivo is discussed.