HIV-1 weaponizes T-cell signals to open nuclear pores and infect resting cells

resting CD4+ T cells are normally resistant to cell-free HIV-1 due to a bottleneck at capsid nuclear import at the nuclear pore, but during cell–cell spread, HIV-1 triggers CD4–LCK signaling that activates CDK1, remodeling nucleoporins and the NPC to boost nuclear import and license infection; this cell–cell spread–driven mechanism explains why resting T cells can be infected in vivo and why cell-free virus is less effective.