Human papillomaviruses biochemical and biologic properties

Abstract

The viral origin of warts and condylomas was established at the beginning of this century by experiments on the transmission of warts by means of cell-free tissue extracts. 1 For a long time, a single virus—the human wart virus—was considered responsible for these lesions, 1 although the multiplicity of human papillomaviruses (HPVs) was suspected on the basis of epidemiologic, 2 serologie, 3 and histologic 4,5 data. It was, thus, generally thought that “the clinical type is determined by the local conditions at the site of infection and not by the virus” 1 and that the clinical evolution of the lesions—in particular, the rare malignant transformation 6,7 of genital condylomas and that of the cutaneous lesions of patients suffering from epidermodysplasia verruciformis (EV)—depended on immunologic, genetic, or extrinsic factors. 1,6,8 The characterization of HPVs and the study of their pathogenic properties have long been hindered by the absence of a cellular system permitting the in vitro replication of these viruses. 9 During the last few years, new methods of analysis of the viral DNA—in particular, the molecular cloning of viral genomes in a plasmid or in the DNA of a bacteriophage—have permitted considerable improvement in our knowledge of HPVs. 10–12 At least 28 HPV types now are recognized 13–29 (Ostrow, R. personal communication). It seems likely that the different clinical types of lesions classically associated with an HPV are, in fact, distinct diseases caused by specific viruses. 23,30–34 Finally, the discovery of the high frequency of infection of the uterine cervix by an HPV, 36,36 as well as the frequent detection of HPV DNA sequences in neoplasias of the skin, 16,32,37–39 the external genitalia, 40–46 and the uterine cervix 24,25 have broadened the spectrum of the pathogenicity of PVs for human beings and imposed the idea that infection by specific HPV types is a risk factor for the development of these neoplasias. After reviewing the physicochemical and biologic characteristics of HPVs and the methods used for their study, we will present recent data on the nomenclature, the pathogenicity, and the oncogenic potential of HPVs.