Monitoring Early Fusion Dynamics of Human Immunodeficiency Virus Type 1 at Single-Molecule Resolution
Open Access
- 15 July 2008
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 82 (14), 7022-7033
- https://doi.org/10.1128/jvi.00053-08
Abstract
The fusion of human immunodeficiency virus type 1 (HIV-1) to host cells is a dynamic process governed by the interaction between glycoproteins on the viral envelope and the major receptor, CD4, and coreceptor on the surface of the cell. How these receptors organize at the virion-cell interface to promote a fusion-competent site is not well understood. Using single-molecule force spectroscopy, we map the tensile strengths, lifetimes, and energy barriers of individual intermolecular bonds between CCR5-tropic HIV-1 gp120 and its receptors CD4 and CCR5 or CXCR4 as a function of the interaction time with the cell. According to the Bell model, at short times of contact between cell and virion, the gp120-CD4 bond is able to withstand forces up to 35 pN and has an initial lifetime of 0.27 s and an intermolecular length of interaction of 0.34 nm. The initial bond also has an energy barrier of 6.7 k B T (where k B is Boltzmann's constant and T is absolute temperature). However, within 0.3 s, individual gp120-CD4 bonds undergo rapid destabilization accompanied by a shortened lifetime and a lowered tensile strength. This destabilization is significantly enhanced by the coreceptor CCR5, not by CXCR4 or fusion inhibitors, which suggests that it is directly related to a conformational change in the gp120-CD4 bond. These measurements highlight the instability and low tensile strength of gp120-receptor bonds, uncover a synergistic role for CCR5 in the progression of the gp120-CD4 bond, and suggest that the cell-virus adhesion complex is functionally arranged about a long-lived gp120-coreceptor bond.Keywords
This publication has 57 references indexed in Scilit:
- What is the biological relevance of the specific bond properties revealed by single‐molecule studies?Journal of Molecular Recognition, 2007
- Electron Tomography of the Contact between T Cells and SIV/HIV-1: Implications for Viral EntryPLoS Pathogens, 2007
- Time Frames for Neutralization during the Human Immunodeficiency Virus Type 1 Entry Phase, as Monitored in Synchronously Infected Cell CulturesJournal of Virology, 2007
- Recombinant Extracellular Domains of Tetraspanin Proteins Are Potent Inhibitors of the Infection of Macrophages by Human Immunodeficiency Virus Type 1Journal of Virology, 2006
- Subunit Stoichiometry of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Trimers during Virus Entry into Host CellsJournal of Virology, 2006
- Stoichiometry of Envelope Glycoprotein Trimers in the Entry of Human Immunodeficiency Virus Type 1Journal of Virology, 2005
- Distinct kinetic and mechanical properties govern selectin-leukocyte interactionsJournal of Cell Science, 2004
- Envelope Glycoprotein Incorporation, Not Shedding of Surface Envelope Glycoprotein (gp120/SU), Is the Primary Determinant of SU Content of Purified Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency VirusJournal of Virology, 2002
- Enhanced Infection of an X4 Strain of HIV-1 Due to Capping and Colocalization of CD4 and CXCR4 Induced by Capsianoside G, a Diterpene GlycosideBiochemical and Biophysical Research Communications, 2001
- Tribute to Bernie GilulaThe Journal of cell biology, 2000