Effects of nucleoside analogues on the expression of herpes simplex type 1-induced proteins

Abstract

Exposure of herpes simplex virus type 1 (HSV-1)-infected Vero cells to the nucleoside analogues 5-iodo-5'-amino-2',5'-dideoxyuridine (AIdUrd), 5-iodo-2'-deoxyuridine (IdUrd) or 5'-amino-2',5'-dideoxythymidine (5'-AdThd) resulted in altered expression of HSV-1-induced proteins. Infected cell proteins (ICPs) synthesized in the presence of the nucleoside analogues were compared by sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis to ICPs from non-drug-treated cells and it was found that there was no effect on HSV-1-induced alpha proteins but beta and gamma proteins were reduced as much as 60%. There were three exceptions: ICP 35 (Mr = 46,000) and ICP 39 (Mr = 36,000) were not reduced and ICP 36 (Mr = 42,000) was increased during drug treatment. Progeny virions were isolated from drug-treated infected Vero cells and were compared to progeny isolated from control cells with respect to their polypeptide make-up and for their ability to induce HSV-1 proteins in non-drug-treated Vero cells. The progeny virus from drug-treated cells exhibited altered protein patterns on SDS-polyacrylamide gels with respect to control HSV-1. The progeny virions from AIdUrd- or IdUrd- but not from 5'-AdThd-treated cells were defective in their abilities to induce proteins upon subsequent infection of non-drug-treated Vero cells. Two unusual phosphoproteins were detected; one with an apparent molecular weight of 30,000 was induced by progeny virus from AIdUrd-treated cells and another at approximately 69,000 was induced by progeny virus from 5'-AdThd-treated cells.