Innovative Workflow Enhances Study of HIV-1 Capsids and Insights for Future Treatments

Recent advancements in microscopy technology have revolutionized our understanding of HIV-1, the most common type of HIV. Researchers at the Salk Institute, led by Associate Professor Dmitry Lyumkis and graduate student Zaida Rodriguez, have developed a novel workflow combining correlative light microscopy and cryo-electron microscopy. This approach allows scientists to observe the structural changes of HIV-1 capsids—protein shells encapsulating the viral genome—over time with unprecedented detail.

HIV-1 capsids play a crucial role in protecting the viral genetic material and enabling the virus to invade host cells. Understanding how these capsids assemble, disassemble, and respond to various pressures is essential for designing effective antiviral strategies. The new workflow captures the morphological transformations of capsids, providing valuable insights into their behavior during the infection process.

This innovative technique addresses the limitations of previous methods, which struggled to visualize structural dynamics at high resolution. Notably, it can be extended to study other viruses' structural changes, opening doors for broader viral research.

The significance of this development is underscored by the therapeutic breakthrough in 2024, when lenacapavir—a drug that targets the HIV capsid to inhibit viral replication—was recognized as the "breakthrough of the year" by Science magazine. While existing drugs focus on disrupting capsid function, a deeper understanding of capsid dynamics could lead to more targeted and effective treatments.

By enabling detailed analysis of capsid stability, formation, and disassembly, this workflow paves the way for identifying new drug targets. It also enhances the capacity to study how structural modifications affect viral infectivity and resistance mechanisms, thereby accelerating the development of next-generation HIV therapies.

The research, published in ACS Nano in August 2025, marks a significant step toward unraveling the complexities of HIV biology. Ultimately, this technological progress offers hope for improved treatments and, potentially, a cure for HIV in the future.

For more information, see the original publication: Zaida K. Rodriguez et al, "Time-Resolved Fluorescence Imaging and Correlative Cryo-Electron Tomography to Study Structural Changes of the HIV-1 Capsid," ACS Nano (2025). Source: https://medicalxpress.com/news/2025-09-hiv-workflow-genome-capsids.html