How HTLV-1 Virus Transforms Immune Cells into Rare Leukemia

An international team has mapped how the HTLV-1 virus causes a rare leukemia in some people. The team, led by Imperial College London and Kumamoto University, used single-cell analysis to reveal that the virus hijacks the activation machinery of T-cells, causing them to persist at a high level of activation, gradually becoming malignant.

Acccording to Yorifumi Satou, co-lead author of the study published today in The Journal of Clinical Investigation, “While only a small percentage of people with HTLV-1 viral infections go on to develop adult T-cell leukemia/lymphoma, there are estimated to be around five to ten million carriers of the virus worldwide, and in some areas it is endemic.”

The HTLV-1 virus inserts itself into one type of T-cell, and, to begin with, remains there in a ‘latent’ state, not releasing any new virus particles or causing any ill effects. For many such carriers of the virus, this never changes, but in around five percent of carriers, after decades of latency the virus reawakens and affects the T-cells’ functioning.

The team studied more than 87,000 T-cells from virus-free donors, healthy carriers of the virus, and patients with ATL. They sequenced the RNA from these cells to find out how the virus and the T-cells were interacting. They revealed that, in people who progressed to ATL, HTLV-1 made infected T-cells highly activated and over-reactive, causing them to over-produce proteins that keep them proliferating and helping them avoid other parts of the immune system that would usually remove rogue cells.

The team thinks that these changes made the overactive T-cells more vulnerable to DNA damage, such as through chemical agents or radiation, accelerating their transition to a cancerous state.

Further study of the processes involved, say the authors, will lay the foundations for potential new treatment options. Co-lead author Masahiro Ono added: “For example, the chronic activation of T-cells could be halted by molecules that block signalling pathways that tell the cells to activate. Alternatively, treatments could target the proteins the activated T-cells create to help them proliferate.”