HIV-1 remodels nuclear pores to infect resting T cells
Updated
Updated · BIOENGINEER.ORG · May 7
HIV-1 remodels nuclear pores to infect resting T cells
10 articles · Updated · BIOENGINEER.ORG · May 7
A Nature study finds cell-to-cell spread triggers CD4-mediated LCK signalling and CDK1 activation, enabling HIV-1 capsids to cross the nuclear envelope in quiescent CD4+ T cells.
Researchers report CDK1-dependent phosphorylation across nucleoporins including Nup54, Nup62 and TPR, suggesting the whole nuclear pore complex acts as a dynamic viral co-factor for nuclear import.
The findings challenge the view that T-cell activation is required for infection and may help explain HIV persistence, integration patterns and why direct cell-to-cell transmission is more efficient than cell-free spread.
A master cell-cycle engine is hijacked by HIV for infection. Could controlling this engine be the key to a functional cure?
If HIV can remodel a cell's nuclear gateway without sounding alarms, what other intruders might be using this secret passage?
HIV was found to pick the lock on a cell's nucleus. Can we now design a drug to permanently jam the keyhole?
The 2026 Paradigm Shift: HIV-1 Nuclear Entry via CDK1-Driven Nuclear Pore Complex Remodeling
Overview
A groundbreaking 2026 study revealed that HIV-1 infects resting CD4+ T cells by exploiting direct cell-to-cell transmission, triggering a signaling cascade involving CD4 receptor engagement, LCK kinase, and CDK1 activation. CDK1 then phosphorylates nucleoporins, remodeling the nuclear pore complex (NPC) to become more permeable, allowing the elastic HIV-1 capsid to pass through. Partial reverse transcription supports this process. After nuclear entry, the capsid gradually uncoats and interacts with host factors like CPSF6, guiding viral DNA integration and establishing a latent reservoir. This discovery overturns previous beliefs about resting T cell resistance and opens new therapeutic avenues targeting these critical steps to prevent or disrupt HIV latency.