The differentiation-dependent life cycle of human papillomaviruses in keratinocytes

Human papillomaviruses (HPVs) are small DNA viruses that induce a variety of hyperproliferative lesions in epithelial tissues. More than 100 different HPV types have been identified and classified on the basis of their nucleotide sequence (Howley and Lowy, 2001). One group of HPVs induces warts on hands or feet and exhibits a high tropism for cutaneous tissues. Another group of HPVs primarily targets genital and oral mucosa. Among these mucosotropic HPVs, types 6 and 11 induce benign lesions and are called "low-risk" HPVs due to their lack of association with cancers. In contrast, HPV types 16, 18, 31, and 45 are referred to as "high-risk" types, since they induce lesions that can ultimately progress to cervical and other cancers (Laimins, 1993; Lowy et al., 1994; zur Hausen, 2002). Despite the differences in oncogenic potential of these various HPV types, it is likely that they share common mechanisms during their productive life cycles.