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Why do viruses cause cancer? Highlights of the first century of human tumour virology
It has been nearly 100 years since Francis Peyton Rous proved that sarcomatous chest tumours in Plymouth Rock hens could be caused by a virus. Since then, seven human viruses have been found to cause 10–15% of human cancers. This Timeline article explores the different techniques that helped in identifying these viruses, the common features they share and the different ways they evade innate immunity and cause cancer.
The year 2011 marks the centenary of Francis Peyton Rous's landmark experiments on an avian cancer virus. Since then, seven human viruses have been found to cause 10–15% of human cancers worldwide. Viruses have been central to modern cancer research and provide profound insights into both infectious and non-infectious cancer causes. This diverse group of viruses reveals unexpected connections between innate immunity, immune sensors and tumour suppressor signalling that control both viral infection and cancer. This Timeline article describes common features of human tumour viruses and discusses how new technologies can be used to identify infectious causes of cancer.
Journal Article
Financial stress and depression in adults: A systematic review
Financial stress has been proposed as an economic determinant of depression. However, there is little systematic analysis of different dimensions of financial stress and their association with depression. This paper reports a systematic review of 40 observational studies quantifying the relationship between various measures of financial stress and depression outcomes in adults. Most of the reviewed studies show that financial stress is positively associated with depression. A positive association between financial stress and depression is found in both high-income and low-and middle-income countries, but is generally stronger among populations with low income or wealth. In addition to the “social causation” pathway, other pathways such as “psychological stress” and “social selection” can also explain the effects of financial stress on depression. More longitudinal research would be useful to investigate the causal relationship and mechanisms linking different dimensions of financial stress and depression. Furthermore, exploration of effects in subgroups could help target interventions to break the cycle of financial stress and depression.
Journal Article
The biology and treatment of Merkel cell carcinoma: current understanding and research priorities
Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer associated with advanced age and immunosuppression. Over the past decade, an association has been discovered between MCC and either integration of the Merkel cell polyomavirus, which likely drives tumorigenesis, or somatic mutations owing to ultraviolet-induced DNA damage. Both virus-positive and virus-negative MCCs are immunogenic, and inhibition of the programmed cell death protein 1 (PD-1)–programmed cell death 1 ligand 1 (PD-L1) immune checkpoint has proved to be highly effective in treating patients with metastatic MCC; however, not all patients have a durable response to immunotherapy. Despite these rapid advances in the understanding and management of patients with MCC, many basic, translational and clinical research questions remain unanswered. In March 2018, an International Workshop on Merkel Cell Carcinoma Research was held at the US National Cancer Institute, at which academic, government and industry experts met to identify the highest-priority research questions. Here, we review the biology and treatment of MCC and report the consensus-based recommendations agreed upon during the workshop.
Journal Article
Clonal Integration of a Polyomavirus in Human Merkel Cell Carcinoma
Merkel cell carcinoma (MCC) is a rare but aggressive human skin cancer that typically affects elderly and immunosuppressed individuals, a feature suggestive of an infectious origin. We studied MCC samples by digital transcriptome subtraction and detected a fusion transcript between a previously undescribed virus T antigen and a human receptor tyrosine phosphatase. Further investigation led to identification and sequence analysis of the 5387-base-pair genome of a previously unknown polyomavirus that we call Merkel cell polyomavirus (MCV or MCPyV). MCV sequences were detected in 8 of 10 (80%) MCC tumors but only 5 of 59 (8%) control tissues from various body sites and 4 of 25 (16%) control skin tissues. In six of eight MCV-positive MCCs, viral DNA was integrated within the tumor genome in a clonal pattern, suggesting that MCV infection and integration preceded clonal expansion of the tumor cells. Thus, MCV may be a contributing factor in the pathogenesis of MCC.
Journal Article
Human oncogenic viruses: nature and discovery
Seven kinds of virus collectively comprise an important cause of cancer, particularly in less developed countries and for people with damaged immune systems. Discovered over the past 54 years, most of these viruses are common infections of humankind for which malignancy is a rare consequence. Various cofactors affect the complex interaction between virus and host and the likelihood of cancer emerging. Although individual human tumour viruses exert their malignant effects in different ways, there are common features that illuminate mechanisms of oncogenesis more generally, whether or not there is a viral aetiology.
This article is part of the themed issue ‘Human oncogenic viruses’.
Journal Article