School of Biomedical Sciences cordially invites you to join the following seminar:

Speaker: Dr. Zhen Hou, Postdoctoral Research Scientist, Division of Structural Biology, Nuffield Department of Medicine, University of Oxford
Talk Title: High-resolution in situ visualisation of HIV-1 nuclear import and its intranuclear trafficking

Date: 7 November 2025 (Friday)
Time: 1:00 pm – 2:00 pm
Venue: Seminar Room 3, G/F, The HKJC Bldg for Interdisciplinary Research, 5 Sassoon Road
Host: Professor Tao Ni

Biography

Dr. Zhen Hou is currently a postdoctoral research scientist in Prof. Peijun Zhang’s lab at STRUBI of University of Oxford, working on the nuclear trafficking of HIV-1 by in-situ cryo-ET. He joined the group in October of 2022, before which he received his PhD training on cryo-EM/ET and biochemistry in Prof. Wolfgang Baumeister’s lab and Prof. Elena Conti’s lab at Max Planck Institute of Biochemistry in Germany. Before moving to Germany, he obtained his bachelor’s degree from the Chinese University of Hong Kong.

Abstract

Human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS, remains a major global health challenge due to its ability to integrate its genome into host chromatin. This integration requires the viral core to traverse the nuclear pore complex (NPC), a highly selective barrier regulating nucleocytoplasmic transport. However, elucidating this process has been hindered by its transient and infrequent nature in infected cells.

Here, we established a robust cell-permeabilization system that faithfully recapitulates HIV-1 nuclear import and developed an integrated cryo-correlative imaging workflow combining cryo-CLEM, cryo-FIB, and cryo-ET. This approach enabled the targeted imaging and structural analysis of nearly two thousand native HIV-1 cores at distinct stages of nuclear import. Our analyses of wild-type and mutant cores revealed that efficient nuclear import depends on both capsid elasticity and NPC plasticity and is modulated by host factors such as CPSF6. Nuclear pores act as selective gates that preferentially accommodate smaller, tube-shaped cores. Furthermore, chromatin analyses revealed that HIV-1 intranuclear trafficking occurs along chromatin-devoid paths and favours regions of less-compact, enriched in dynamically positioned nucleosomes, likely corresponding to transcriptionally active domains involved in replication and RNA processing. Together, these findings define the structural and mechanistic interplay between the HIV-1 capsid, NPC, and chromatin, providing a framework for understanding nuclear import and its connection to uncoating and integration.

ALL ARE WELCOME.