Making a virtue of necessity: the pleiotropic role of human endogenous retroviruses in cancer

Author:

Kassiotis George12ORCID,Stoye Jonathan P.32ORCID

Affiliation:

1. Retroviral Immunology, The Francis Crick Institute, London, UK

2. Department of Medicine, Faculty of Medicine, Imperial College London, London, UK

3. Retrovirus–Host Interactions, The Francis Crick Institute, London, UK

Abstract

Like all other mammals, humans harbour an astonishing number of endogenous retroviruses (ERVs), as well as other retroelements, embedded in their genome. These remnants of ancestral germline infection with distinct exogenous retroviruses display various degrees of open reading frame integrity and replication capability. Modern day exogenous retroviruses, as well as the infectious predecessors of ERVs, are demonstrably oncogenic. Further, replication-competent ERVs continue to cause cancers in many other species of mammal. Moreover, human cancers are characterized by transcriptional activation of human endogenous retroviruses (HERVs). These observations conspire to incriminate HERVs as causative agents of human cancer. However, exhaustive investigation of cancer genomes suggests that HERVs have entirely lost the ability for re-infection and thus the potential for insertional mutagenic activity. Although there may be non-insertional mechanisms by which HERVs contribute to cancer development, recent evidence also uncovers potent anti-tumour activities exerted by HERV replication intermediates or protein products. On balance, it appears that HERVs, despite their oncogenic past, now represent potential targets for immune-mediated anti-tumour mechanisms. This article is part of the themed issue ‘Human oncogenic viruses’.

Funder

Wellcome Trust

Publisher

The Royal Society

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology

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