Unique mechanical properties of the HIV-1 core and their biological role

The HIV-1 core is a conical structure encasing two copies of the viral genomic RNA. During the virus lifecycle, the core must satisfy varying and often conflicting mechanical requirements. Upon entry, the core must remain structurally intact to protect its cargo and enable efficient reverse transcription. Conversely, to infect the target cell, the core should undergo spatiotemporally accurate disassembly to release the reverse transcribed genome into the cell’s nucleus for integration. In addition, recent evidence suggests that the cores must enter the cell nucleus through the narrow nuclear pore while remaining intact. Taken together, the core appears to have unique mechanical properties to suffice all the above requirements. Using AFM, we previously characterized the transitioning of the core stiffness and morphology during reverse transcription (RT). Here we characterize the elastic properties of HIV-1 cores prior and during RT. We find that the core has the ability to undergo reversible extensive deformation without undergoing any structural failure. However, the core’s elasticity is reduced and the ability to maintain structural integrity drastically reduces with the progression of reverse transcription. Our data provide a mechanical mechanism that allow the core to squeeze into the nuclear pore without damaging its structure followed by RT induced disassembly.