A Stiffness Switch in HIV

¹ Weizmann Institute of Science
² University of Utah
³ Ben-Gurion University of the Negev

^* To whom correspondence should be addressed. E-mail: itay.rousso{at}weizmann.ac.il.

Submitted on July 23, 2006
Revised on September 1, 2006
Accepted on 21 November 2006

	Abstract

Following budding from the cell, 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 nano-indentation 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 8-fold 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 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 lifecycle (i.e., stiff during viral budding vs. 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.

Key Words: AFM, HIV, Membrane fusion, Virion assembly, mechanical properties

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