Modulation of herpes simplex virus (HSV) infection of cultured neuronal cells by nerve growth factor and antibody to HSV

Abstract

Cultures of neonatal rat dorsal root ganglia (DRG) and the rat phaeochromocytoma line PC12 were used to study herpes simplex virus type 1 (HSV)-neuronal cell interactions. Cultures were used for HSV infection either without additional treatment, or with pretreatment with nerve growth factor (NGF), or with subsequent exposure to medium containing neutralizing antibody to HSV or with a combination of NGF and antibody. The appearance of morphological changes in the cultured cells following HSV infection was delayed by treatment with NGF or neutralizing antibody alone. Both treatments given concurrently resulted in maximal delay; similar results were obtained for both PC12 and DRG cultures. The appearance of a variety of HSV-specified polypeptides identified by a polyspecific rabbit anti-HSV antibody and monoclonal antibodies to the product of immediate early (IE) gene 3, Vmw175 (1098 and 58S), to the major DNA binding protein (1147), to glycoprotein C, gC (1001), and of a minor heat shock protein (identified by monoclonal antibody T156), was followed after HSV infection by indirect immunofluorescence. Staining with polyspecific rabbit anti-HSV increased with time after infection both in intensity and extent and correlated well with the degree of the morphological changes. This staining was delayed by NGF treatment, by exposure to neutralizing antibody, and maximally by both treatments combined, the DRG and PC12 behaving very similarly. Labelling with monoclonal antibodies 1098, 58S and 1147 was increased and that with antibody 1001 decreased in PC12 cells by NGF treatment. No such increased labelling with 1098 was observed in DRG cultures after NGF treatment. It is proposed that NGF treatment leads to increased expression of Vmw175 and to a delay in the transition from early to late HSV polypeptide synthesis in PC12 cells. The expression of the cellular stress protein defined by T156 was upregulated after HSV infection. This upregulation was most marked in cultures treated with NGF.