Novel Imaging Technique Reveals Key to Targeting Blood Cancer Virus

Researchers at the University of Minnesota’s School of Dentistry and Masonic Cancer Center have made a significant breakthrough in understanding the structure of the human T-cell leukemia virus (HTLV), a retrovirus that causes adult T-cell leukemia/lymphoma. The findings, published in Nature Communications, could pave the way for the development of the first effective treatments for this challenging disease.

Unveiling the Virus’s Structure

HTLV, related to HIV, currently has no cure. The research team, led by Wei Zhang, an associate professor in the School of Dentistry and Masonic Cancer Center, and Louis Mansky, director of the Institute for Molecular Virology and a professor in the School of Dentistry, Masonic Cancer Center, employed cryogenic transmission electron microscopy and tomography (cryo-EM/ET) to visualize the virus’s capsid protein – the protective shell surrounding its genetic material. Cryo-EM/ET involves rapidly freezing samples to extremely low temperatures before imaging, producing high-resolution, 3D images of cellular structures.

Why the Capsid Protein Matters

The capsid protein is a crucial target for antiviral therapies. Researchers have successfully used similar techniques to develop treatments for HIV, making it a promising avenue for HTLV research. The study successfully used the cryo-EM/ET process to study the capsid protein’s structure, providing a powerful tool for structure-based drug design.

Key Findings of the Study

• For the first time, researchers mapped how the virus assembles and reproduces.
• Measurements of the distance between the capsid protein and the outer layer of the virus provide insights into the protein’s distribution within the virus particle.
• The research identified that a negatively charged molecule required for building HIV particles can similarly be used, though is not essential, for HTLV, offering a potential target for drug development.

Implications for Treatment Development

“These high-resolution images will be useful for helping us understand why HTLV infectivity is strongly correlated with being associated with cells, where virus spread occurs through direct cell-to-cell contact,” explained Mansky. “This remains a long-standing question in the field and could help guide the design of treatments for HTLV infection – a highly important task, knowing there are currently no such approved therapeutics.”

The team plans to continue researching how the HTLV capsid protein contributes to virus particle formation and to identify potential antiviral drugs that could disrupt this process.

Collaboration and Funding

This research was a collaborative effort involving researchers from the University of Minnesota, the University of Delaware, and the University of Central Florida. Funding was provided by the National Institutes of Health and the Masonic Cancer Center, University of Minnesota.

About the University of Minnesota School of Dentistry

The University of Minnesota School of Dentistry is dedicated to advancing health through scientific discovery, education, and high-quality patient care. As the only dental school in the state, it educates future oral health professionals and provides consultation services to five states. Approximately 72% of Minnesota’s practicing dentists are graduates of this school. The school’s clinics see over 156,000 patient visits annually. Learn more at dentistry.umn.edu.