Cancer-causing virus HTLV-1 changes DNA loops to ‘affect tens of thousands of genes’

June 26, London, Cambridge – Researchers at Imperial College London and the European Bioinformatics Institute (EMBL-EBI) have shown that the human T-lymphotropic virus (HTLV-1) changes the folding pattern of human DNA in infected cells. They explain that the resulting disruption of gene function increases the risk of leukaemia.

The research, published in the journal eLife, shows that the human leukaemia virus (HTLV-1) acts at a large number of sites across the human genome, disrupting the regulation of tens of thousands of genes.

Asymptomatic vs symptomatic

HTLV-1 is thought to infect more than 10 million people around the world. The virus can be transmitted through unprotected sex, blood transfusions, and from mother to baby via breast milk.

People can carry the virus for decades without symptoms, and 90% of people may be unaware they are carrying it at all. However, an estimated 5-10% of those infected may go on to develop an aggressive form of leukaemia or a progressive paralytic disease.

In the latest study, researchers looked at how HTLV-1 interacts with human DNA when it infects a host, focusing on its target: specialised white blood cells called T-cells.

Disrupting chromatin loops

Each human cell contains around two metres of DNA, neatly packaged into the nucleus. In order to fit, these twisting strands are tightly coiled and then wrapped around proteins, creating a densely packed genetic spaghetti structure called chromatin.

The chromatin is not randomly organised, but is folded into thousands of loops, which stick out from the main ‘strand’. These loops expose certain regions of DNA to the cell’s machinery that reads and copies DNA, enabling specific chunks of the genome to be more easily read and transcribed.

Recent research has shown that disrupting these existing loops, or creating new loops, alters the control of gene expression and may be linked to a host of diseases.

The research team isolated T-cells from HTLV-1-infected patients and analysed which regions of the DNA were altered. They found that the virus binds to a protein called CTCF, which is the key protein that forms normal loops in the human genome. As a result, the virus changes the structure of the loop and the activity of genes within it.

“Through binding to these specific sites in the genome, retroviruses like HTLV-1 can alter chromatin loops and disrupt how a number of important genes are regulated,” explains Professor Charles Bangham, Chair of immunology in the Department of Medicine at Imperial College London and lead author of the study. “This can lead to the abnormalities and disease, such as the leukaemia associated with HTLV-1.”

“This study illustrates that by combining wet lab and dry lab expertise, we can explore previously inaccessible biological processes,” adds Ewan Birney, Director of the European Bioinformatics Institute (EMBL-EBI) and paper co-author. “By integrating complex genomic data – in this case haplotype-resolved data – into our analysis, we have gained new insights into how the human T-cell leukaemia virus works. In turn, this could help us understand why certain patients experience such devastating symptoms, while others are asymptomatic.” 

Read the full press release on the Imperial college London website.