Françoise Breitburd

Specificity of cytopathic effect of cutaneous human papillomaviruses

Abstract Papillomaviruses are highly tissue-specific, and are characterized by a specific mode of interaction with the squamous epithelia they infect. 1 It has been proposed that this interaction presents two successive steps that depend on the stage of differentiation of the host cell in the wart. In the basal germinal cells the viral replication is never observed. Based on the well-studied model of the papillomas induced by the Shope cottontail rabbit papillomavirus, it is most likely that the viral genome is present in the basal cells as a small number (10 to 50) of extrachromosomal copies. 2,3 The viral messenger RNAs expressed correspond to nonstructural viral proteins, as yet unidentified, but most probably involved in the altered response of basal cells to the mechanisms regulating their mitotic rate and the size of the germinal cell population, thus resulting in the formation of a papilloma. 4 Vegetative viral DNA replication is triggered upon the onset of the terminal differentiation process in the suprabasal layers, followed by the synthesis of viral structural proteins and the assembly of viral particles in more superficial layers. 1,4

Regulation of MHC Class I, Class II and ICAM-1 Expression by Cytokines and Retinoids in HPV-Harboring Keratinocyte Lines

The growth and progression of HPV-associated,potentially malignant anogenital. lesions seems to be controlled by local. immunosurveillance mechanisms. These mechanisms include tumor antigen presentation, tumor cell recognition and eradication by specific T cytotoxic lymphocytes (Chen et al., 1992) and natural. cytotoxic cells (Malejczyk et al., 1989). The immune recognition and cytolysis are dependent, in a part, on the expression on effector/target cells of some adhesion molecules, eg.LFA-l/ICAM-1 and CD2/LFA-3 receptor/ligand pairs, as well as class I and class II MHC-glycoproteins reacting with CD8 and CD4 molecules, respectively.

Release of Soluble Tumor Necrosis Factor-α (TNF-α) Receptor by HPV-Associated Neoplastic Cells

There is a growing evidence that immunological. system is involved in surveillance against HPV-associated neoplasia.1 The immune mechanisms responsible for eradication of HPV-induced tumors may include direct participation of natural. killer (NK) cells,2 activated macrophages,3 and cytotoxic T lymphocytes.4Furthermore, growth and dissemination of potentially malignant lesions may be under control of locally released im-munoregulatory anti-tumor cytokines including interferons,5 inter Ieukin-6, transforming growth factor-β,7 as well as tumor necrosis factor-α (TNF-α).8