The genetic material of HIV-1 is packaged inside a cone shaped container that is called the viral core. To infect a cell, the viral core must pass through the cell’s nuclear pore. Using atomic force microscopy, a technique that uses a tiny needle to feel the surface of things at the microscopic level, and molecular dynamic simulations, we discovered that wild-type HIV-1 cores quickly revert to their normal shape after compression, while capsid mutants with impaired nuclear entry are brittle. Restoring elasticity in these mutants recovered their ability to infect. Treatment with capsid-targeting drugs also reduced core elasticity. These findings suggest that capsid elasticity is essential for HIV-1 nuclear entry and infection, offering new insights into HIV-1 mechanics and potential antiviral strategies.
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