Human papillomaviruses: a growing field

Abstract

A combination of functional studies on human papillomavirus (HPV) oncoproteins and epidemiological studies on persistence of HPV infection firmly established a role for HPV in the etiology of cervical cancers. Understanding the viral life cycle of HPVs has been more difficult. In this issue of Genes & Development, Wang et al. (pp. 181 - 194) describe an efficient method to propagate infectious HPV in differentiating epithelium, providing clear evidence for temporal separation of viral and cellular replication.

Figure 1.

Organotypic culture of human papillomavirus. PHKs are either transfected with plasmids that recombine in vivo to give circularized HPV18, or the PHKs are infected with HPV18 virions produced from organotypic cultures of HPV18-transfected PHKs. The PHKs are placed on a collagen-fibroblast matrix, lifted (“rafted”) when confluent and grown for 10–14 d. E7 induces the subrabasal cells to remain in cycle and cellular DNA replication occurs; the HPV genome remains a low-copy episome. When cellular DNA synthesis is complete, there is a brief pseudo-S-like or G2-like phase, in which viral DNA replication occurs. The high levels of E2 repress E6/E7 transcription, turning off the markers of S phase, re-expressing p130, and allowing late gene transcription, capsid assembly, and the final stages of epithelial differentiation.