Effects of 5-iodo-2'-deoxyuridine on ultrastructural localization of viral antigens in cultured cells infected with herpes simplex virus.

Changes in viral morphology and localization of viral antigens induced by 5-iodo-2'-deoxyuridine (IDU) were studied using herpes simplex virus-infected monolayers of cultured rabbit corneal cells. A direct antibody enzyme method was employed for immunoelectron and light microscopy. There was no significant difference between the control and the IDU groups in the intracellular distribution of antigen up to 2 hours after infection. At 2 hours after infection, intracytoplasmic antigen began to appear in control and IDU-treated cells either in patchy distributions or in association with rough endoplasmic reticulum. Intranuclear staining appeared also at 2 hours after infection as a diffuse fine granular reaction. At 3 hours after infection, the intracytoplasmic reaction became more or less diffuse and there was slightly more cytoplasmic staining in the untreated group. At 6 hours after infection, reaction products increased in the cytoplasm and the nuclei in both groups but IDU-treated cells showed less intracytoplasmic and more intranuclear staining. The nuclear envelope was stained positive in both groups but IDU-treated cells showed a decreased reaction in the cytoplasmic membranous structure and fewer reaction deposits on the cell surface. At 12 and 18 hours after infection, the intranuclear accumulation of reaction products after IDU treatment became more evident. Progeny virus particles were significantly fewer in the presence of IDU: Nucleocapsids were found but in a greatly reduced number and only one incompletely enveloped particle was found. The morphology of the individual nucleocapsid, however, was not significantly altered by treatment with IDU. The preponderance of reaction substances in the nuclei compared to the cytoplasm in treatment groups may reflect distorted protein synthesis and may provide morphological evidence of the biochemical hypothesis of IDU efficacy: IDU exerts its antiviral effects through abnormal protein synthesis and the resultant defects in capsid assembly. Decreased reaction substances in the membranous structures of the cytoplasm may be related to reduced or abnormal production of envelope-associated viral antigens.