Oncogenic spiral by infectious pathogens: Cooperation of multiple factors in cancer development.

Chronic infection is one of the major causes of cancer, and there are several mechanisms for infection-mediated oncogenesis. Some pathogens encode gene products that behave like oncogenic factors, hijacking cellular pathways to promote the survival and proliferation of infected cells in vivo. Some of these viral oncoproteins trigger a cellular damage defense response leading to senescence; however, other viral factors hinder this suppressive effect, suggesting that cooperation of those viral factors is important for malignant transformation. Coinfection with multiple agents is known to accelerate cancer development in certain cases. For example, parasitic or bacterial infection is a risk factor for adult T-cell leukemia-lymphoma induced by human T-cell leukemia virus type 1, and Epstein-Barr virus and malaria are closely associated with endemic Burkitt lymphoma. Human immunodeficiency virus type 1 infection is accompanied by various types of infection-related cancer. These findings indicate that these oncogenic pathogens can cooperate to overcome host barriers against cancer development. In this review, the authors focus on the collaborative strategies of pathogens for oncogenesis from two different points of view: (i) the cooperation of two or more different factors encoded by a single pathogen; and (ii) the acceleration of oncogenesis by coinfection with multiple agents.