Virus‐Induced Human Oncogenesis

Abstract

Infectious agents are estimated to contribute to oncogenesis in c. 25% of human cancers worldwide. Approximately half of them are attributed to infection by oncogenic viruses. Viruses are obligatory intracellular pathogens, which disrupt host cell homeostasis during their life cycle. The induction of malignancy is not part of their life cycle, but rather a multistep outcome, that may occur several years after the infection. Oncogenesis is initiated by the disruption of cellular mechanisms (detecting and repairing DNA damage, activating checkpoints and inducing apoptosis or survival) through the activity of viral proteins. Host and environmental factors further contribute to the multistep aetiology of cancer development and progression. This article describes the common molecular mechanisms by which human oncogenic viruses disrupt cell homeostasis and the prophylactic and therapeutic treatment options for virus‐induced malignancies and discusses the identification of emerging oncogenic infectious agents.

Key Concepts

  • Oncogenic viruses are estimated to contribute to approximately 15% of all human malignancies.
  • Human oncogenic viruses include both DNA viruses (EBV, HPV, MCV, HBV and KSHV) and RNA viruses (HCV and HTLV‐1).
  • Induction of malignancy is not part of the viral life cycle and confers no benefit to the virus per se.
  • Oncogenic viruses disrupt host cellular pathways (DNA repair mechanisms, cellular checkpoints and apoptosis) for efficient viral replication, consequently initiating cancer development.
  • Viral oncogenesis is a multi‐step process, initiated by the action of viral proteins but requiring additional factors for disease development and progression.
  • Transmission of oncogenic viruses takes place mainly via human contact including, but not limited to, sexual transmission.
  • Prophylactic (vaccine) treatment options are limited. Therapeutic treatments include anti‐virals in combination with chemotherapy and surgical removal of the tumours.
  • Emerging oncogenic viruses comprise a growing group of newly identified viruses with putative oncogenic potential, which have been detected in association with human cancers.

Keywords: oncogenic viruses; cancer; DNA virus; RNA virus; EBV ; HPV ; HBV ; HCV ; HTLV‐I ; KSHV ; MCV

Figure 1. Overview of molecular mechanisms that facilitate viral replication and promote cancer initiation. Latent or chronic infections by oncogenic viruses are associated with viral modulation of cellular pathways, which facilitate efficient viral replication, albeit with oncogenic consequences for the infected host. The viruses modulating each pathway are indicated. The modulation of these cellular pathways, via the activity of the indicated viral proteins, confers specific cancer hallmarks (Hanahan and Weinberg, ) to the infected cells. The colour code indicates the respective viral proteins of each virus: EBV – orange, HBV – blue, HCV – red, HPV – green, HTLV‐1 – brown, KSHV – purple, MCV – turquoise.
Figure 2. Schematic overview of the signalling pathways modulated upon infection by oncogenic viruses, in order to sustain proliferative signalling of the infected cell. The viral proteins and their cellular targets are indicated. Colour code, indicating each virus and its proteins, as in Figure. Host proteins are indicated in black.
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Bedi, Manmeet S, and Ploubidou, Aspasia(Jun 2015) Virus‐Induced Human Oncogenesis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021851.pub2]