ROLE OF MACROPHAGES IN PAPILLOMAVIRUS INF ECTIONS

Papillomaviruses have naturally a strict tropism to epithelial cells i n which they replicate during the cell differentiation. There is no hi stological evidence of any inflammatory reaction. No leucocyte recrute ment is observed and thus, the role of macrophages during the early in fectious process in the epithelium remains unknown. This silent, subac ute or chronic infectious disease is characterized fundamen tally by a dual pathogenic process, including an infectious process leading to t he production of infective virus particles during the differentiation of infected epithelial cells, on the one hand, and an oncogenic proces s due to interactions of viral oncogenes with host cell regulatory pro teins after integration of the virus to the cellular genome. The role of activated macrophages on the oncogenic process is clearly establish ed. They contribute to regulate negatively the transcription of the no n structural-E6 E7 viral oncogenes and have cytotoxic effects to trans formed cells by a direct intercellular contact without evidence of an effect due to a soluble factor such as tumor-necrotizing factor (TNF). Macrophages have, hence, a prominent role as cellular effecters of pr otective immunity against lesions due to papillomaviruses and particul arly against the oncogenic process complicating these infections.