Viruses and Human Cancers: a Long Road of Discovery of Molecular Paradigms

Abstract

SUMMARY About a fifth of all human cancers worldwide are caused by infectious agents. In 12% of cancers, seven different viruses have been causally linked to human oncogenesis: Epstein-Barr virus, hepatitis B virus, human papillomavirus, human T-cell lymphotropic virus, hepatitis C virus, Kaposi's sarcoma herpesvirus, and Merkel cell polyomavirus. Here, we review the many molecular mechanisms of oncogenesis that have been discovered over the decades of study of these viruses. We discuss how viruses can act at different stages in the complex multistep process of carcinogenesis. Early events include their involvement in mutagenic events associated with tumor initiation such as viral integration and insertional mutagenesis as well as viral promotion of DNA damage. Also involved in tumor progression is the dysregulation of cellular processes by viral proteins, and we describe how this has been investigated by studies in cell culture and in experimental animals and by molecular cellular approaches. Also important are the molecular mechanisms whereby viruses interact with the immune system and the immune evasion strategies that have evolved.

Prevalence of Neurotropic Viruses in Malignant Glioma and Their Onco-Modulatory Potential

“…Viruses evade host immune responses and a variety of these strategies have been discussed elsewhere (9). In a similar manner, tumours overcome immune surveillance during their malignant progression, as has also been demonstrated in the case of EBV infection, which is present in about 90% of the world population.…”

“…In their recent review, White et al indicated at least seven viruses that have been causally linked to human oncogenesis, stating that viruses can be involved in both tumour initiation and tumour progression (9). In general, DNA viruses affect cells by binding of the viral proteins to tumour-suppressor genes, and they also produce dsRNA-binding proteins that can act as suppressors of RNA silencing, thereby favouring tumour development.…”

“…there is seropositivity among the population, it has been difficult to establish any associations between viral infections and CNS malignancy based on epidemiology alone (9). The HSV-1, HSV-2, HCMV, and HHV-6 human herpes viruses are currently attracting much attention as possible factors in initiating human brain tumours (11).…”

Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection

“…The mechanisms by which EBV and HHV-8 may foster carcinogenesis are complex and not fully understood [31,32]. In both cases, common viral infections cause rare malignancies; this highlights the potential contribution of multifactorial nonviral factors to the development of infection-related cancer.…”

“…EBV establishes long-term latent infections in B cells and may act just as an initial promoter of cellular transformation from which subsequent progression to cancer is independent [31,32]. The dominant EBV latency patterns observed in non-Hodgkin lymphoma tissue differ between pre- [33] and post-cART studies [34].…”