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Open Access Highly Accessed Research

Virion stiffness regulates immature HIV-1 entry

Hong-Bo Pang13, Liron Hevroni2, Nitzan Kol2, Debra M Eckert1, Marianna Tsvitov2, Michael S Kay1* and Itay Rousso24*

Author Affiliations

1 Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112-5650, USA

2 Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel

3 Present address: Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA

4 Present address: Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva 84105, Israel

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Retrovirology 2013, 10:4  doi:10.1186/1742-4690-10-4

Published: 10 January 2013

Abstract

Background

Human immunodeficiency virus type 1 (HIV-1) undergoes a protease-mediated maturation process that is required for its infectivity. Little is known about how the physical properties of viral particles change during maturation and how these changes affect the viral lifecycle. Using Atomic Force Microscopy (AFM), we previously discovered that HIV undergoes a “stiffness switch”, a dramatic reduction in particle stiffness during maturation that is mediated by the viral Envelope (Env) protein.

Results

In this study, we show that transmembrane-anchored Env cytoplasmic tail (CT) domain is sufficient to regulate the particle stiffness of immature HIV-1. Using this construct expressed in trans with viral Env lacking the CT domain, we show that increasing particle stiffness reduces viral entry activity in immature virions. A similar effect was also observed for immature HIV-1 pseudovirions containing Env from vesicular stomatitis virus.

Conclusions

This linkage between particle stiffness and viral entry activity illustrates a novel level of regulation for viral replication, providing the first evidence for a biological role of virion physical properties and suggesting a new inhibitory strategy.

Keywords:
HIV; Viral entry; Atomic force microscopy; Maturation; Stiffness