Early Damage of Herpes-Infected Cells by Antibody-Dependent Cellular Cytotoxicity: Relative Roles of Virus-Specified Cell-Surface Antigens and Input Virus

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Abstract
Previous studies in our laboratory indicated that tissue culture cells acutely infected with type 1 herpes simplex virus (HSV) could be recognized at 2 hr post-infection (PI) by antibody-dependent cellular cytotoxicity (ADCC) and damaged by ADCC at 3 hr PI. Since the design of these studies did not preculde the possibility that damage occurs even earlier in the infectious cycle, we performed the present series of experiments to assess this possibility as well as to gauge the relative contributions of virus-specified cell-surface antigens and input virus in rendering target cells susceptible to cytotoxic attack. When present during both the first 2 hr of infection as well as during the following 4-hr ADCC assay period, both actinomycin D (1 µg/ml), an inhibitor of RNA synthesis, and cycloheximide (5 µg/ml), an inhibitor of protein synthesis, strongly reduced the cytotoxic reaction (by 70 and 90%, respectively). The inhibitory effects of these agents indicate that the bulk, but not all, of the ADCC reaction was directed at target cells synthesizing virus-specified surface antigens. Between 10 and 30% of the injured cells were attacked because of input virus that had not penetrated the target cell. This was shown by a) the small portion of ADCC that resisted actinomycin D and cycloheximide, b) the biphasic ADCC kinetic reaction curve of target cells exposed to antibody and effector cells immediately after virus adsorption, and c) the small but reproducible cytotoxic reaction against target cells exposed to virus inactivated by ultraviolet light. A small portion of the infected cell population could be injured by ADCC within the first hour after viral adsorption due to input virus.