Infectious agents can contribute to malignant transformation by several mechanisms. These can be broadly divided into: chronic inflammation, which drives abnormal levels of cell proliferation (yellow); direct virus-induced transformation of infected cells, leading to increased cell survival (red); and immunosuppression, which allows the pathogen to evade the immune system and persist (blue). The colour coding is maintained from Figure 1. Chronic inflammation leads to the production of inflammatory cytokines as well as reactive oxygen and nitrogen oxide species (ROS and RNOS) by phagocytes at the site of infection, which can lead to DNA damage as well as cellular damage and increased cell cycling. Virus-induced transformation is caused by the actions of pathogen-encoded oncogenic proteins as well as by integration into the host genome (HPV). The transforming events outlined in this figure do not necessarily lead directly to cancer formation; for example, despite encoding similar proteins, other infectious agents do not cause cancer. The fact that some pathogens have evolved to persist without causing tumorigenesis also highlights that persistence is maybe a prerequisite for, but is on its own insufficient for, oncogenesis in humans. Immune evasion mechanisms include control of the adaptive and innate immune system, allowing avoidance of tumor surveillance. EBV, Epstein-Barr virus; HBV, human hepatitis virus B; HCV, hepatitis virus C; HIV, human immunodeficiency virus; HPV, human papillomavirus; HTLV-1, human T-lymphotropic virus 1; KSHV, Kaposi sarcoma-associated herpesvirus.
Dalton-Griffin and Kellam Journal of Biology 2009 8:67 doi:10.1186/jbiol168