# HTLV-1, Tax and HBZ in adult T-cell leukaemia/lymphoma

Source: https://onco.cc/terms/lymphoma-bio-htlv1/  
OnCo record `lymphoma-bio-htlv1` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A virus passed mostly from mother to child in breast milk, common in parts of Japan, the Caribbean, west Africa and South America. Most people who carry it never become ill, but in a few it causes an aggressive T-cell cancer decades later.

## Summary

Human T-lymphotropic virus 1 integrates into the DNA of a CD4 T cell and stays there. Two of its genes matter. Tax switches on NF-kB and interferes with the DNA damage response and the spindle checkpoint, which is how the infected clone starts to expand and to accumulate damage; it is also the most visible protein to the immune system, so clones that silence it survive. HBZ, encoded on the opposite DNA strand, is kept on when Tax is switched off and sustains proliferation more quietly.

What the host genome then acquires is not random. Across 426 cases analysed by whole-genome, exome, transcriptome and targeted sequencing with copy-number and methylation arrays, the alterations overlapped significantly with the set of proteins Tax itself binds, and were concentrated in T-cell receptor and NF-kB signalling, T-cell trafficking and immune surveillance: activating mutations in PLCG1, PRKCB, CARD11, VAV1, IRF4, FYN, CCR4 and CCR7, CTLA4-CD28 and ICOS-CD28 fusions, and intragenic deletions of IKZF2, CARD11 and TP73 (Kataoka 2015). The virus, in other words, starts the process and the cell finishes it along the lines the virus drew.

The practical consequence is CCR4. It is both frequently expressed and frequently mutated in this disease, and mogamulizumab, the anti-CCR4 antibody, is used because of it. The virus itself is not a drug target and antiviral treatment does not cure the leukaemia. Transmission is mainly through breastfeeding, and the interval between infection in infancy and the disease is measured in decades, which is why screening and formula feeding in endemic regions is a prevention question rather than a treatment one.

## Fields

- Kind: Term
- Last checked: 2026-09-30
- Also known as: HTLV-1; Human T-lymphotropic virus 1; Tax; HBZ; ATLL

## Sources

- Kataoka et al., Nat Genet 2015: integrated molecular analysis of 426 adult T-cell leukaemia/lymphoma cases: https://doi.org/10.1038/ng.3415
- Kim et al., Lancet Oncol 2018: MAVORIC, mogamulizumab against vorinostat in previously treated cutaneous T-cell lymphoma: https://doi.org/10.1016/S1470-2045(18)30379-6

## Connected records

- cancers: [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)](https://onco.cc/cancers/peripheral-t-cell-lymphoma/)
- targets: [CARD11](https://onco.cc/targets/card11/), [CCR4](https://onco.cc/targets/ccr4/), [CD52](https://onco.cc/targets/cd52/), [IRF4](https://onco.cc/targets/irf4/), [PLCG1](https://onco.cc/targets/plcg1/), [VAV1](https://onco.cc/targets/vav1/)
- pathways: [Inflammation & NF-κB](https://onco.cc/pathways/inflammation-nfkb/), [Oncogenic viruses](https://onco.cc/pathways/oncogenic-viruses/)
- terms: [Epstein-Barr virus latency programmes, and why they decide which lymphoma](https://onco.cc/terms/lymphoma-bio-ebv-latency/)

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