Around 10 million people globally live with the life-threatening virus HTLV-1. Yet it remains a poorly understood disease that currently has no preventative treatments and no cure.
But a landmark study co-led by Australian researchers could change this, after finding existing HIV drugs can suppress transmission of the HTLV-1 virus in mice.
The study, published in Cell, could lead to the first treatments to prevent the spread of this virus that is endemic among many First Nations communities around the world, including in Central Australia.
The research by WEHI and the Peter Doherty Institute for Infection and Immunity (Doherty Institute) also identifies a new drug target that could lead to the elimination of HTLV-1 positive cells from those with an established infection, and prevent disease progression.
At a glance
- New research co-led by WEHI and the Doherty Institute could lead to the first preventative treatments for HTLV-1, one of the most complex and neglected viruses in the world.
- The study found two specific HIV antivirals already on the market can suppress transmission of HTLV-1 in humanised mice and prevent disease, identifying the first prophylactic treatment against HTLV-1.
- Secondly, when the HIV antivirals were used in combination with a compound that induces cell death, infected cells were killed – flagging a potential future curative strategy for the disease.
- The unprecedented findings could enable these drugs to enter clinical trials preventing establishment of pathogenic levels of HTLV-1.
Human T-cell leukaemia virus type 1 (HTLV-1) is a virus that infects the same cell type as HIV – T cells, a type of blood immune cell that helps the body fight off infections.
A small proportion of people infected with HTLV-1 after a long duration of infection develop serious diseases, such as adult T-cell leukemia and spinal cord inflammation.
Co-lead author and WEHI laboratory head Dr Marcel Doerflinger said the promising results of the new study could help find a desperately needed treatment and prevention strategy for one of the most neglected viruses in the world.
"Our study marks the first time any research group has been able to suppress this virus in a living organism," Dr Doerflinger said.
"As HTLV-1 symptoms can take decades to appear, by the time a person knows they have the infection the immune damage is already in full swing.
"Suppressing the virus at transmission would allow us to stop it before it has the chance to cause irreversible damage to immune function, leading to disease and a premature death."
In a research effort spanning 10 years, the collaborative team isolated the virus and developed a world-first humanised mouse model for HTLV-1 that enabled them to study how the virus behaves in a living organism with a human-like immune system.
The mice were transplanted with human immune cells that are susceptible to HTLV-1 infections, including with Australia's genetically novel HTLV-1 strain. International and Australian strains equally caused leukaemia and inflammatory lung disease in these human immune system mice.
The mice were then treated with tenofovir and dolutegravir – two antiviral therapies currently approved to silence HIV and prevent AIDS. The team discovered both drugs could also powerfully suppress HTLV-1.
"What's most exciting is that these antivirals are already in use for millions of HIV patients, meaning there's a direct path for the clinical translation of our findings," Dr Doerflinger said.
"We won't have to start from scratch because we already know these drugs are safe and effective. And now we've shown that their use can very likely be extended to HTLV-1."
In another remarkable finding, the team discovered that human cells containing HTLV-1 could be selectively killed when mice were treated with HIV drugs in combination with another therapy inhibiting a protein (MCL-1) known to help rogue cells stay alive.
The team is now leveraging precision RNA therapies to develop new ways to target MCL-1 and establish combination treatments that can be clinically tested, which they believe could offer a promising curative strategy for HTLV-1.
Crucial insight
The development of the humanised mouse models central to this study at WEHI was spearheaded by first author Dr James Cooney and Professor Marc Pellegrini, study lead author, WEHI Honourary Fellow and Executive Director at Centenary Institute.
Prof Pellegrini said the mouse models were not only critical in identifying potential therapeutic targets, but also allowed researchers to understand how different strains of the HTLV-1 virus can alter disease symptoms and outcomes. This is particularly important for the unique strain that is present in Australia, HTLV-1c.
"It's long been hypothesised that differences in viral subtype may influence disease outcomes, but a lack of research into HTLV-1 has made it difficult for us to find the evidence needed to support this claim – until now.
"Our study provides critical insights that enable us to better understand the consequences of the distinct molecular make-up of the virus affecting our First Nations communities. This will further help us to investigate ways to create the tools needed to control the spread of this virus subtype."
The human HTLV-1 samples needed to develop the mouse models were obtained through the front-line clinical work of Associate Professor Lloyd Einsiedel, a Clinician Scientist at the Doherty Institute and Infectious Diseases Physician, who has provided a clinical service to Central Australia for more than a decade and has dedicated his career to putting HTLV-1 on the map.
Advocacy for a neglected disease
Research by the University of Melbourne's Professor Damian Purcell, Head of Molecular Virology at the Doherty Institute and co-lead author of the study, isolated the virus from First Nations donors and identified significant genetic differences between the HTLV-1c strains from Central Australia compared to the HTLV-1a strains found internationally.
The new findings show that both HTLV-1 strains cause disease in mice, with HTLV-1c showing more aggressive features. The identified drug therapies were found to be equally effective against both strains.
Prof Purcell and Associate Prof Lloyd Einsiedel worked with the National Aboriginal Community Controlled Health Organisation (NACCHO) HTLV-1 committee and the Australian Department of Health over many years to advocate for guidance on HTLV-1 from the World Health Organization (WHO) that led to them formally classify the virus as a Threatening Pathogen to Humans in 2021.
This resulted in the development of formal WHO policies to reduce transmission internationally and the development of clinical management guidelines for HTLV-1c in Central Australia under NACCHO leadership.
"Despite Australia's high burden of HTLV-1, the virus and its associated diseases are still not notifiable in most states and true infection rates in the nation remain unknown," Prof Purcell said.
"People at risk from HTLV-1 deserve biomedical tools like those that provide game-changing therapeutic and prevention options for other blood-borne persistent viral infections, such as HIV.
"There is a real opportunity to prevent the transmission of HTLV-1 and end the diseases caused by these infections. Our research findings are a major leap forward in this."
The research team is currently in talks with the companies behind the HIV antivirals used in this study, to see if HTLV-1 patients can be included in their ongoing clinical trials. If successful, this would pave the way for these drugs to become the first approved pre-exposure prophylaxis against HTLV-1 acquisition.
These findings are supported by The Australian Centre for HIV and Hepatitis Virology Research, The Phyllis Connor Memorial Trust, Drakensberg Trust and the National Health and Medical Research Council (NHMRC).
The study, "Combination antiretroviral therapy and MCL-1 inhibition mitigate HTLV-1 infection in vivo", is published in Cell (DOI: 10.1016/j.cell.2025.06.023 ).
