Papillomavirus proteins and their potential as drug design targets

The papillomaviruses are a family of small, double-stranded DNA viruses that infect the basal cells of cutaneous and mucosal epithelium. While a large percentage of the population is benignly infected with various strains of human papillomavirus (HPV), long-term infection by a subset of HPV strains is associated with malignant transformation. The prospects for prophylaxis against HPV infection have recently received an enormous boost with the approval by the US FDA of a vaccine targeted against the most common cancer-associated HPV strains. However, the large number of people already infected, the high cost of the vaccination regimen (particularly in poorer countries) and the HPV infections that these vaccines do not protect against underscore the need for therapeutic strategies. The elucidation of molecular details underlying fundamental processes in the viral life cycle, such as virus replication, transcription and HPV-induced carcinogenesis, is required to meet this aim. This article provides an overview of high-resolution structures of papillomavirus proteins and their functional complexes, with particular reference to mechanistic and structural features that could be exploited in the rational design of antiviral agents.