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* Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel; Department of Mechanical Engineering and Department of Materials Engineering, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel; and Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, Utah 84112-5650
Correspondence: Address reprint requests to Itay Rousso, Dept. of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel. Tel.: 972-8-9343479; Fax: 972-8-9344136; E-mail: itay.rousso{at}weizmann.ac.il; or Michael S. Kay, Dept. of Biochemistry, University of Utah School of Medicine, 15 N. Medical Drive East Rm. 4100, Salt Lake City, UT 84112-5650. Tel.: 801-585-5021; Fax: 801-581-7959; E-mail: kay{at}biochem.utah.edu.
After budding from the cell, human immunodeficiency virus (HIV) and other retrovirus particles undergo a maturation process that is required for their infectivity. During maturation, HIV particles undergo a significant internal morphological reorganization, changing from a roughly spherically symmetric immature particle with a thick protein shell to a mature particle with a thin protein shell and conical core. However, the physical principles underlying viral particle production, maturation, and entry into cells remain poorly understood. Here, using nanoindentation experiments conducted by an atomic force microscope (AFM), we report the mechanical measurements of HIV particles. We find that immature particles are more than 14-fold stiffer than mature particles and that this large difference is primarily mediated by the HIV envelope cytoplasmic tail domain. Finite element simulation shows that for immature virions the average Young's modulus drops more than eightfold when the cytoplasmic tail domain is deleted (930 vs. 115 MPa). We also find a striking correlation between the softening of viruses during maturation and their ability to enter cells, providing the first evidence, to our knowledge, for a prominent role for virus mechanical properties in the infection process. These results show that HIV regulates its mechanical properties at different stages of its life cycle (i.e., stiff during viral budding versus soft during entry) and that this regulation may be important for efficient infectivity. Our report of this maturation-induced "stiffness switch" in HIV establishes the groundwork for mechanistic studies of how retroviral particles can regulate their mechanical properties to affect biological function.
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