Scientists have made a breakthrough in understanding the structure of Human T-cell Leukemia Virus Type 1 (HTLV-1), a lesser-known cousin of HIV. Using cutting-edge imaging technology, researchers from the Institute of Science and Technology Austria (ISTA), in collaboration with the University of Minnesota and Cornell University, have unveiled unique features of HTLV-1’s architecture that set it apart from other retroviruses.
Summary: Researchers have revealed the distinct architectural features of HTLV-1, a virus related to HIV, using advanced imaging techniques. This discovery could lead to new treatment strategies for HTLV-1 infections.
Estimated reading time: 6 minutes
The Overlooked Cousin of HIV
HTLV-1 belongs to the same family of retroviruses as HIV-1 but has received less attention from the scientific community. Florian Schur from ISTA explains, “HTLV-1 is somewhat the overlooked cousin of HIV. It has a lower prevalence than HIV-1, yet there are many cases around the world.”
Despite its lower profile, HTLV-1 poses a significant health threat. The World Health Organization estimates that between 5 and 10 million people are currently living with HTLV-1. While most infections remain asymptomatic, approximately 5% lead to aggressive diseases such as adult T-cell leukemia/lymphoma, a form of cancer with a poor prognosis.
Martin Obr, a postdoc in Schur’s research group, emphasizes the importance of studying HTLV-1: “As a human pathogen causing severe diseases, HTLV-1 should be at the forefront of our research to address the questions about its functions and structure.”
Unraveling the Viral Lattice
The researchers focused on understanding the structure of the HTLV-1 virus particle, particularly in its immature form. Schur explains, “When a virus gets produced, it generates a particle. This particle, however, is not yet infectious. The immature virus particle must undergo a maturation process to become infectious.”
Using Cryo-Electron Tomography (Cryo-ET), a high-resolution imaging technique, the team discovered that the lattice of immature HTLV-1 is remarkably different from other retroviruses. The virus particles are shaped by a lattice of proteins arranged into a spherical shell, which protects the viral genetic material until it infects a host cell.
A Unique Architectural Design
The analysis revealed that HTLV-1’s building blocks are assembled in a unique fashion, resulting in a distinct overall architecture. Obr notes, “We were expecting a difference from other viruses, but the extent of it completely blew us away.”
One key difference lies in how the lattice is held together. In most retroviruses, the lattice consists of a top and bottom layer, with the bottom layer acting as the “glue” that maintains structural integrity. However, in HTLV-1, this arrangement is reversed. Schur explains, “In HTLV, it’s the other way around. The bottom layer is basically just hanging by a thread.”
This unique structure may be linked to HTLV-1’s transmission method. Unlike HIV-1, which uses cell-free transmission, HTLV-1 prefers direct contact between infected and uninfected cells. Obr speculates, “From an evolutionary standpoint, it was probably advantageous for HTLV-1 to change its lattice structure for this kind of transmission. Nevertheless, at this point, it is only speculation. It needs to be experimentally verified.”
Implications for Future Treatments
Understanding HTLV-1’s structural details opens up new possibilities for treatment approaches. Schur outlines potential strategies: “There are types of viral inhibitors that disrupt the assemblies by targeting the building blocks to prevent them from coming together. Others work by destabilizing the lattice. There are many possibilities.”
The research team used non-infectious virus-like particles to study HTLV-1 safely. These particles were produced in cell cultures and closely resemble the actual immature virus. Obr assures, “Our virus-like particles only lack a few enzymes that would help them to mature. There is no reason to think the real immature particle does look different.”
This groundbreaking research, published in Nature Structural & Molecular Biology, provides a solid foundation for future studies on HTLV-1 and potential therapeutic interventions.
Quiz
- What is the estimated number of people living with HTLV-1 worldwide?
- What percentage of HTLV-1 infections lead to aggressive diseases?
- What imaging technique did the researchers use to study HTLV-1’s structure?
Answer Key:
- Between 5 and 10 million people
- Approximately 5%
- Cryo-Electron Tomography (Cryo-ET)
Further Reading:
- World Health Organization on HTLV-1: https://www.who.int/news-room/fact-sheets/detail/human-t-lymphotropic-virus-type-1
- Introduction to Cryo-Electron Tomography: https://www.nature.com/articles/s41592-019-0591-8
- Retrovirus Structure and Assembly: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778513/
Glossary of Terms:
- HTLV-1: Human T-cell Leukemia Virus Type 1, a retrovirus related to HIV.
- Retrovirus: A type of virus that uses RNA as its genetic material and can integrate into the host’s DNA.
- Cryo-Electron Tomography (Cryo-ET): A high-resolution imaging technique used to study biological structures in their native state.
- Lattice: In virology, a regular arrangement of protein subunits that forms the structure of a virus particle.
- Immature virus particle: A newly formed virus particle that is not yet infectious and must undergo further changes to become fully functional.
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