ALTERED PATTERN OF GROWTH AND DIFFERENTIATION IN HUMAN KERATINOCYTES INFECTED BY SIMIAN VIRUS-40

Human epidermal keratinocytes were infected by simian virus 40 in vitro. The structure of the developing keratinocyte colony reflects the spatial separation of cell division and keratinization in intact skin; thymidine-incorporating cells were primarily localized at the colony periphery whereas nondividing, histologically differential cells accumulated in the interior. Viral infection produced a dramatic increase in the size of the proliferative population as, simultaneously differentiation was reduced in the colony interior. These changes were manifest when simian virus 40 T-antigen synthesis was detectable in only a small percentage of the cells; differentiation became increasingly density dependent as the percentage of T-antigen-positive cells rose over serial passage. The disruption of the normal pattern of growth/differentiation localization coincided with a loss of dependence on serum for growth, but preceded the appearance of other virus-induced properties associated with transformation, i.e., the ability to form colonies in soft agar and independence of growth from fibroblasts.