Bursting HIV’s bubble: A new workflow to study HIV-1 genome-containing capsids
image: From left: Timothy Strutzenberg, Zaida Rodriguez, Dmitry Lyumkis, and Leonardo Andrade.
Credit: Salk Institute
Background: 40 million people live with HIV globally, and that number continues to rise. While therapies exist to reduce the amount of HIV in a patient’s body and, in turn, reduce HIV symptoms, there remains no cure. Engineering better drugs and eventually a cure depends on our ability to answer foundational questions like: How does HIV invade and replicate in host cells?
New findings: Salk Institute scientists, led by Associate Professor Dmitry Lyumkis and graduate student researcher Zaida Rodriguez, developed an improved workflow for characterizing capsids (genome-containing protein cones) in HIV-1 (the most common form of HIV). HIV-1 capsids protect the viral genome and enable host cell invasion. The new workflow uses correlative light and cryo-electron microscopy techniques to capture the morphological changes of HIV-1 capsids over time. The findings were published in ACS Nano on August 22, 2025.
Why this is important: In 2024, the drug lenacapavir, which blocks viral replication by altering the HIV-1 capsid structure, was deemed the breakthrough of the year by Science magazine. Still, structural studies of how capsids form, disassemble, and stabilize have been restricted by workflow and technology limitations. This novel workflow incorporates advanced technology that will allow scientists to better understand how capsid morphology changes in response to distinct pressures and to pinpoint new, more effective ways to target capsids and treat HIV-1. Importantly, the workflow can also be used to study structural changes in other, non-HIV viruses.
Other authors: Atousa Mehrani, Leonardo Andrade, and Timothy Strutzenberg of Salk; Jonathan Andino-Moncada, Ahinsa Ranaweera, Jincheng Shi, Satya Prakash Singh, Scott Stagg, and Ashwanth Francis of Florida State University; Sergey Buth, Mariana Marin, Ricardo Guerrero-Ferreira, and Gregory Melikyan of Emory University School of Medicine; and Hamid Rahmani and Danielle Grotjahn of Scripps Research Institute.
Funding: This work was supported by the National Institutes of Health (NIAID U54 AI170855, NIAID R01 AI129862, NIAID R01 AI150998, U01 AI136680, R01 AI184419, NIAID 1R21AI174879, F32GM148049, T32 GM133351), Margaret T. Morris Foundation, Hearst Foundations, NOMIS Foundation, Pew Scholars Program, Scripps Research, and Irwin Jacobs Innovation and Collaboration Grant.
About the Salk Institute for Biological Studies: Unlocking the secrets of life itself is the driving force behind the Salk Institute. Our team of world-class, award-winning scientists pushes the boundaries of knowledge in areas such as neuroscience, cancer research, aging, immunobiology, plant biology, computational biology, and more. Founded by Jonas Salk, developer of the first safe and effective polio vaccine, the Institute is an independent, nonprofit research organization and architectural landmark: small by choice, intimate by nature, and fearless in the face of any challenge. Learn more at www.salk.edu.