Australian researchers have achieved a major breakthrough in the fight against HTLV-1, identifying the first potential prophylactic treatments for a virus that affects approximately 10 million people worldwide yet remains largely neglected by the medical community. The landmark study, published in Cell and co-led by WEHI and the Peter Doherty Institute for Infection and Immunity, demonstrates that existing HIV antivirals can suppress HTLV-1 transmission in humanized mice.
Breakthrough in HTLV-1 Suppression
The research team discovered that tenofovir and dolutegravir, two antiviral therapies currently approved for HIV treatment and AIDS prevention, could powerfully suppress Human T-cell leukaemia virus type 1 (HTLV-1) in their novel mouse model. This marks the first time any research group has been able to suppress this virus in a living organism.
"Our study marks the first time any research group has been able to suppress this virus in a living organism," said Dr. Marcel Doerflinger, co-lead author and WEHI laboratory head. "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."
Novel Humanized Mouse Model Development
The breakthrough was made possible through a decade-long research effort that resulted in the development of a world-first humanized mouse model for HTLV-1. The mice were transplanted with human immune cells susceptible to HTLV-1 infections, including Australia's genetically novel HTLV-1c strain. Both international HTLV-1a strains and the Australian HTLV-1c strain equally caused leukemia and inflammatory lung disease in these humanized mice.
The development of these mouse models was spearheaded by first author Dr. James Cooney and Professor Marc Pellegrini, study lead author and WEHI Honorary Fellow. Professor Pellegrini emphasized the importance of understanding different viral strains: "It's long been hypothesized 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."
Dual Therapeutic Approach Shows Promise
Beyond prophylactic potential, the research revealed a promising curative strategy. When HIV antivirals were combined with compounds that inhibit MCL-1, a protein that helps rogue cells survive, the treatment could selectively kill human cells containing HTLV-1. This combination approach represents a potential pathway to eliminate HTLV-1-positive cells from those with established infections and prevent disease progression.
The team is now leveraging precision RNA therapies to develop new ways to target MCL-1 and establish combination treatments for clinical testing.
Clinical Translation Pathway
The use of already-approved HIV medications provides a direct path to clinical application. "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 explained. "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."
The research team is currently in discussions with pharmaceutical companies behind the HIV antivirals to include HTLV-1 patients in ongoing clinical trials. Success in these negotiations could pave the way for these drugs to become the first approved pre-exposure prophylaxis against HTLV-1 acquisition.
Addressing a Neglected Global Health Challenge
HTLV-1 infects the same T cells targeted by HIV but has received significantly less research attention despite affecting millions globally. The virus is particularly endemic among First Nations communities worldwide, including in Central Australia. A small proportion of infected individuals develop serious diseases after long-duration infections, including adult T-cell leukemia and spinal cord inflammation.
Professor Damian Purcell, Head of Molecular Virology at the Doherty Institute and co-lead author, highlighted the ongoing challenges: "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. 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."
Strain-Specific Insights
The research provided critical insights into how different HTLV-1 strains affect disease outcomes. Professor Purcell's work isolated the virus from First Nations donors and identified significant genetic differences between HTLV-1c strains from Central Australia compared to internationally found HTLV-1a strains. The study showed both strains cause disease in mice, with HTLV-1c displaying more aggressive features, though the identified drug therapies proved equally effective against both strains.
Global Health Impact
The research has already contributed to significant policy changes. Professor Purcell and Associate Professor Lloyd Einsiedel worked with the National Aboriginal Community Controlled Health Organisation (NACCHO) HTLV-1 committee and the Australian Department of Health to advocate for World Health Organization guidance on HTLV-1. This advocacy led to the WHO formally classifying the virus as a Threatening Pathogen to Humans in 2021, resulting in formal WHO policies to reduce transmission internationally and clinical management guidelines for HTLV-1c in Central Australia.
The unprecedented findings represent a major leap forward in addressing one of the world's most neglected viruses, offering hope for both prevention and treatment of HTLV-1 infections that currently have no approved therapeutic options.
