New research from the University of Minnesota School of Dentistry and Masonic Cancer Center is providing important new insights into the structure of a human virus that causes blood cancer. The findings were recently published in Nature Communications.
The research team, led by Wei Zhang, an associate professor in the School of Dentistry, Masonic Cancer Center, and Louis Mansky, director of the Institute for Molecular Virology and a professor in the School of Dentistry, Masonic Cancer Center, analyzed human T-cell leukemia virus (HTLV), a human retrovirus that causes adult T-cell leukemia/lymphoma and is related to HIV. As there is no current treatment for this disease, the research team used high-resolution imaging of the virus to help uncover where therapies might be successful.
The researchers used cryogenic transmission electron microscopy and tomography (cryo-EM/ET) - imaging techniques that produce high-resolution, 3D images of cellular structures by rapidly freezing samples to extremely low temperatures before imaging - to examine the HTLV capsid protein. A capsid protein is the shell that surrounds a virus, protects its genetic material and plays a crucial role in its molecular assembly. This is a promising target for treating HTLV because researchers recently successfully used this method to treat HIV.
The study found:
- Using the cryo-EM/ET process, researchers are successfully able to study the capsid protein's structure - a powerful tool that can help develop structure-based drug designs.
- For the first time, researchers were able to identify how the virus is assembled and reproduced. In one example, researchers measured the distance between the capsid protein and the outer layer of the virus which provides information about how the capsid protein is distributed within the virus particle.
- The team found that a specific negatively charged molecule required for building HIV particulars can be used, but is not required, to also treat HTLV. This could inform drug design as this is a location where investigational drugs bind for HIV.
"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. 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," said Mansky.
The team plans to conduct further research to study how the HTLV capsid protein helps to build virus particles and identify how therapeutics, such as antiviral drugs, could be directed to interfere with this process.
The University of Minnesota team collaborated with researchers at the University of Delaware and the University of Central Florida on this study. This research was supported by funding from the National Institute of Health and the Masonic Cancer Center, University of Minnesota.
