Researchers at Queen Mary University of London, in collaboration with University College London, have identified a previously unrecognised mechanism by which HIV-1 infects resting immune cells, addressing a long-standing gap in understanding viral entry in vivo. Their study, published in Nature, builds on the established observation that HIV spreads efficiently through direct cell-to-cell contact between T cells.
The key novelty of the work lies not in the mode of transmission itself, but in how infection is achieved in otherwise non-permissive resting cells. The authors show that during CD4-mediated cell contact, HIV triggers intracellular signalling that induces a tightly controlled, low-level activation of CDK1, a central regulator of the cell cycle. Rather than driving cell division, this restrained CDK1 activity is repurposed to remodel the nuclear pore complex, enabling viral genomes to access the nucleus without triggering full T cell activation.
Reflecting on the finding, UCL author Professor Rob de Bruin commented that “the idea that HIV can exploit a restrained pool of CDK1 to remodel the nucleus without triggering division is astonishing and fundamentally changes how we think about infection of resting immune cells.”
Beyond HIV, the study suggests that nuclear pore function may be dynamically regulated by cell-cycle kinases in response to external signalling, raising the possibility that other viruses could exploit similar mechanisms.
The work identifies potential therapeutic opportunities by targeting virus-induced CD4 signalling or CDK1-dependent nuclear entry steps early in infection.