HIV and HERVs
Posted by Henry Bauer on 2014/06/13
Etienne de Harven has suggested how “Human Endogenous Retroviruses can resolve HIV/AIDS puzzles”. Our friend and colleague Mo A. alerted us to this highly pertinent article:
J Virol. 2014 Jun 11. pii: JVI.00919-14. [Epub ahead of print]
Unfixed endogenous retroviral insertions in the human population.
Marchi E1, Kanapin A2, Magiorkinis G3, Belshaw R4.
1 Department of Zoology, University of Oxford, Oxford OX1 3PS, UK.
2 The Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK.
3 Department of Zoology, University of Oxford, Oxford OX1 3PS, UK
4 School of Biomedical and Healthcare Sciences, Plymouth University, Plymouth PL4 8AA, UK email@example.com
One lineage of human endogenous retroviruses, HERV-K(HML2), is upregulated in many cancers, some autoimmune/inflammatory diseases, and in HIV-infected cells. Despite three decades of research it is not known if these viruses play a causal role in disease, and there has been recent interest in whether they can be used as immunotherapy targets. Resolution of both these questions will be helped by an ability to distinguish between the effects of different integrated copies of the virus (loci). Research so far has concentrated on the 20 or so recently integrated loci that, with one exception, are in the human reference genome sequence. However, this viral lineage has been copying in the human population within the last million years, so some loci will inevitably be present in the human population but absent from the reference sequence. We therefore performed the first detailed search for such loci by mining whole genome sequences generated by Next Generation Sequencing. We found a total of 17 loci: ranging from being present in only two of the 358 individuals examined to being present in over 95% of them. On average, each individual had six loci that are not in the human reference genome sequence. Comparing the number of loci we found to an expectation derived from a neutral population genetic model suggests that the lineage was copying till at least ∼250,000 years ago.
About 5% of our genome sequence is composed of the remains of retroviruses that over millions of years have integrated into the chromosomes of egg and/or sperm precursor cells. There are indications that protein expression of these viruses is higher in some diseases, and we need to know (a) whether these viruses have a role in causing disease and (b) whether they can be used as immunotherapy targets in some of them. Answering both questions requires a better understanding of how individuals differ in the viruses they carry. We therefore carried out the first careful search for new viruses in some of the many human genome sequences that are now available thanks to advances in sequencing technology. We also compare the number we find to a theoretical expectation to see if it is likely that these viruses are still replicating in the human population today.
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
PMID: 24920817 [PubMed – as supplied by publisher]