A specific signature of Merkel cell polyomavirus persistence in human cancer cells

Abstract

Presently, slightly >20% of the global cancer incidence has been linked to viral, bacterial, and parasitic infections (1). Some of these agents act as direct carcinogens, where persistence and expression of viral oncogenes are required to maintain the malignant phenotype of the cancer cells; others act indirectly, e.g., by inducing immunosuppression or chronic inflammation or activating oxygen- or nitroso-radicals. Commonly, in direct carcinogenesis the genomes of oncogenic viruses persist, being either integrated into host cell DNA or as episomes within the cancer cells. Under specific conditions viral DNA may become reactivated (Epstein–Barr virus, human T lymphotropic retrovirus, human herpesvirus type 8), resulting in complete cycles of viral replication. High-risk human papillomaviruses often acquire partial deletions of their genomes in the course of viral integration into host cell DNA, and some of the persisting Epstein–Barr virus genomes may become replication-defective in Burkitt's lymphoma cells. In hepatitis B virus-linked carcinogenesis integrated viral DNA fragments may persist in an apparently random pattern.