More than just oncogenes: mechanisms of tumorigenesis by human viruses

Abstract

Most humans are infected with at least one of the known human cancer viruses during their lifetimes. While the initial infection with these viruses does not cause major disease, infected cells can acquire cancer hallmarks, particularly upon immunosuppression or exposure to co-carcinogenic stimuli. Even though cancer formation represents a rare outcome of a viral infection, approximately one out of eight human cancers has a viral etiology. Viral cancers present unique opportunities for prophylaxis, diagnosis, and therapy, as demonstrated by the success of HBV and HPV vaccines and HCV antivirals in decreasing the incidence of tumors that are caused by these viruses. Here we review common characteristics and mechanisms of action of the human oncogenic viruses.

Figure 1:

Schematic representation on the interplay of viral (blue) and cellular (red) factors that can contribute to human carcinogenesis. All of the human cancer viruses establish persistent infections, where the virus has managed to reprogram the infected host cell and subvert antiviral defense responses. Viral proteins that serve to reprogram the host cell and blunt antiviral responses often have oncogenic activities. These activities include inhibition of cell death, enhanced proliferation and induction of genomic instability. Inflammatory responses to viral infection produce reactive oxygen species that can drive carcinogenesis by inducing genomic instability and also stimulate proliferation to replaced damaged tissue. Most infections with human oncogenic viruses do not lead to carcinogenesis, and malignant progression generally requires exposure to co-carcinogenic factors. While in many cases virus-associated cancers remain addicted to viral oncoprotein expression, in other cases viruses may only contribute to specific stages of carcinogenesis (“oncomodulatory” viruses) and viral sequences may be lost in the cancer cells (“hit-and-run” carcinogenesis).