The Role of Human Endogenous Retroviruses (HERV-K) in the Pathogenesis of Human Cancers

Review Article

William Simmons

Abstract

Transmission of oncogenic retroviruses demonstrated in 1908. Much work was done around that period since by other researchers who demonstrated transfer of Sarcoma in chickens through filtrates. Although the name ‘retroviruses’ was coined as late as 1974, retroviral diseases were distinguished much earlier. Human endogenous retroviruses (HERVs) are natural components of the human genome and are considered remnants of ancient germ line infections by exogenous retroviruses. The human genome sequencing project revealed that 8 to 9% of the human genome is of retroviral origin. About 800 of these elements (class II HERVs) are beta-retrovirus-like and therefore distantly related to exogenous MMTV (an accepted aetiological agent for mammary tumour in mice). The majority of HERVs are noninfectious and replication-defective retroviral fossils. Some members of each HERV family however have been found to still be transcriptionally active. Furthermore, tissue-specific HERV expression profiles could be established for all human tissues investigated so far, confirming that HERVs are permanent components of the human transcriptome. A prevalence of HERV transcripts, in particular class II elements, such as members of the HML-2 family have been reported for various cancer tissues. In this review we focus our attention therefore on the association of class II HERVs with cancers. We also discuss the importance of this group of HERVs to humans, their relationship with other triggering factors (e.g. other viruses); and if there is to date a definitive causal role in cancer. We outlined the future perspectives with respect to HERVs and its contribution to human cancers, the methods of diagnosing and prognosticating; and plans to forestall attendant disease linked to these viruses by vaccine route, for example. The active sub-species purported to cause diseases in humans are the HERV-K and HERV-W.

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