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 differentiated 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.