A Retrovirus Stiffness Switch

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DESCRIPTION (provided by applicant): After budding from the cell, retroviruses (such as HIV) undergo a complex spontaneous process called maturation that is required for their infectivity. During maturation retroviruses undergo dramatic internal reorganization. These changes have been extensively characterized in HIV by biochemical and electron microscopy methods. Very recently, atomic force microscopy (AFM) measurements have revealed a dramatic decrease in virion stiffness during maturation ("stiffness switch"). Interestingly, this stiffness switch is largely controlled by the viral envelope (Env) protein, which also mediates the ability of virions to enter target cells. The proposed studies will dissect the mechanism of the HIV stiffness switch and determine how Env regulates this switch. Current data suggests a correlation between virion stiffness and entry activity. The proposed studies will also determine if viral mechanical properties directly control viral entry activity. Such a novel regulatory mechanism would reveal a previously unappreciated layer of complexity in the retrovirus life-cycle and will have broader implications for mechanical regulation of other complex biological systems.