Peijun Zhang
Nuffield Department of Medicine, University of Oxford and Electron Bio-Imaging Centre (eBIC), Diamond Light Source, UK
The Tale of the HIV-1 Capsid: From Assembly to Nuclear Transport
Retroviruses, including human immunodeficiency virus type 1 (HIV-1), contain a capsid that encloses the viral RNA genome. After cell entry, the capsid traverses the cytoplasm and delivers the viral genome to the nucleus, where it is integrated into host chromatin. Throughout the viral life cycle, the capsid surface serves as a critical interface between the virus and the host, mediating interactions with host restriction factors and viral dependency factors. It is also a major target for antiviral drug development, as exemplified by the long-acting inhibitor lenacapavir. In this presentation, I will discuss HIV-1 capsid assembly and its interactions with host factors, including inositol hexakisphosphate (IP6), with an emphasis on interactions essential for capsid stabilization. I will also highlight our recent in situ structural studies of HIV-1 nuclear transport and discuss the architecture of native chromatin fibres in intact T cells in the context of HIV-1 infection.
Selected references
1. Hou Z, Shen Y, Shen J, Chen L, Stuart DI, Zhang P* (2025) In situ chromatin dynamics and HIV-1 nuclear trafficking. bioRxiv DOI:10.64898/2025.12.12.693995
2. Hou Z, Fronik S, Shen Y, Chen L, Thompson C, Neumann S, Zhang P* (2025) Direct visualization of HIV-1 core nuclear import and its interplay with the nuclear pore. EMBO Rep 26(21):5133-5153
3. Hou Z, Shen Y, Fronik S, Shen J, Shi J, Xu J, Chen L, Hardenbrook N, Engelman AN, Aiken C, Zhang P* (2025) HIV-1 nuclear import is selective and depends on both capsid elasticity and nuclear pore adaptability. Nat Microbiol 10(8):1868-1885
4. Zhu Y, Kleinpeter AB, Rey JS, Shen J, Shen Y, Xu J, Hardenbrook N, Chen L, Lucic A, Perilla JR, Freed EO, Zhang P* (2025) Structural basis for HIV-1 capsid adaption to a deficiency in IP6 packaging. Nat Commun 16(1):8152
5. Ni T, Zhu Y, Yang Z, Xu C, Chaban Y, Nesterova T, Ning J, Böcking T, Parker MW, Monnie C, Ahn J, Perilla JR, Zhang P* (2021) Structure of native HIV-1 cores and their interactions with IP6 and CypA. Sci Adv 7(47):eabj5715
6. Ni T, Gerard S, Zhao G, Dent K, Ning J, Zhou J, Shi J, Anderson-Daniels J, Li W, Jang S, Engelman AN, Aiken C, Zhang P* (2020) Intrinsic curvature of HIV-1 CA hexamer underlies capsid topology and interaction with cyclophilin A. Nat Struct Mol Biol 27(9):855-862