Linkage of regression and malignant conversion of rabbit viral papillomas to MHC class II genes

HUMAN papillomaviruses associated with cutaneous 1 and ano-genital 2 cancers induce intraepithelial precursor lesions which may regress spontaneously or progress into invasive carcinomas 3,4 . Cell-mediated immune responses are probably involved in regression of precancerous lesions 1,5–8 and the polymorphism of the genes responsible may thus have a key role in the variability of the host response. Skin warts and cancers induced in rabbits by Shope papillomavirus 9–12 provide a model to test this hypothesis. We analysed a restriction-fragment-length polymorphism of major histocompatibility complex class I and class II genes 13,14 and T-cell receptor β -chain genes 15 in infected domestic rabbits. We found a strong linkage between wart regression and a DRαEco RI fragment, and an increased relative risk of malignant transformation associated with a DQα Pvu II fragment. This indicates a genetic control of wart evolution, involving genes in the class II region of the major histocompatibility complex.