Latent papillomavirus infections and their regulation.

Model systems show that papillomavirus DNA can persist after lesion-regression, and be maintained in a subset of epithelial basal cells. These are very likely long-lived 'stem-cells' or 'stem-like cells', with latency arising via at least two distinct mechanisms. The first involves low-titre virus infection and the retention of viral DNA at levels that are too low to allow life-cycle completion. The second involves lesion-formation, and clearance by the adaptive immune system, followed by persistence with low-level viral gene expression, and possible reactivation upon immune depletion. Mechanical irritation, inflammation and other extracellular influences affect viral copy number in the latently infected cell, and may predispose to lesion-reappearance. Reactivation may account for the recurrence of 'apparently cleared' cervical lesions caused by high-risk types, the appearance of Beta HPV-lesions following immunosuppression, and the development of recurrent respiratory papillomatosis in afflicted children. Crown