Single-Molecule Analysis of Human Immunodeficiency Virus Type 1 gp120-Receptor Interactions in Living Cells

Chang, Melissa I.; Panorchan, Porntula; Dobrowsky, Terrence M.; Tseng, Yiider; Wirtz, Denis

doi:10.1128/jvi.79.23.14748-14755.2005

Cited by 68 publications

(73 citation statements)

References 44 publications

(45 reference statements)

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“…This observation suggests a more complex energy landscape of the underlying interaction, presumably with more than one barrier and pathway. This type of interaction was observed previously for HIV (24). However, the structural origin and shape of the second energy barrier remains to be elucidated by SVFS at higher loading rates.…”

Section: Discussionsupporting

confidence: 48%

Influenza virus binds its host cell using multiple dynamic interactions

Sieben

Kappel

Zhu

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

130

102

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Influenza virus belongs to a wide range of enveloped viruses. The major spike protein hemagglutinin binds sialic acid residues of glycoproteins and glycolipids with dissociation constants in the millimolar range [Sauter NK, et al. (1992) Biochemistry 31:9609-9621], indicating a multivalent binding mode. Here, we characterized the attachment of influenza virus to host cell receptors using three independent approaches. Optical tweezers and atomic force microscopy-based single-molecule force spectroscopy revealed very low interaction forces. Further, the observation of sequential unbinding events strongly suggests a multivalent binding mode between virus and cell membrane. Molecular dynamics simulations reveal a variety of unbinding pathways that indicate a highly dynamic interaction between HA and its receptor, allowing rationalization of influenza virus-cell binding quantitatively at the molecular level.multivalency | adhesion | avidity | tropism

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Section: Discussionsupporting

confidence: 48%

Influenza virus binds its host cell using multiple dynamic interactions

Sieben

Kappel

Zhu

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

130

102

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“…32,41 For moderate, physical values of receptor concentrations and degradation, the average time to entry is relatively constant across a large range of parameters.…”

Section: Resultsmentioning

confidence: 99%

“…41 More important are the physical properties of the cellular system such as the receptor diffusion coefficient, receptor concentration, and the magnitude and acting mechanism of the degradation rate. These are all independent of viral properties (15) and may perhaps help explain why certain cell types are more susceptible to HIV-1 entry.…”

Section: Discussionmentioning

confidence: 99%

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Diffusion-Dependent Mechanisms of Receptor Engagement and Viral Entry

2010

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Enveloped viruses attach to host cells by binding to receptors on the cell surface. For many viruses, entry occurs via membrane fusion after a sufficient number of receptors have engaged ligand proteins on the virion. Under conditions where the cell surface receptor densities are low, recruitment of receptors may be limited by diffusion rather than by receptor-ligand interactions. We present a receptor-binding model that includes the effects of receptor availability at the viral binding site. The receptor binding and unbinding kinetics are coupled to receptor diffusion across the cell membrane. We find numerical solutions to our model and analyze the viral entry probabilities and the mean times to entry as functions of receptor concentration, receptor diffusivity, receptor binding stoichiometry, receptor detachment rates, and virus degradation/detachment rates. We also show how entry probabilities and times differ when receptors bind randomly or sequentially to the binding sites on the viral glycoprotein spikes. Our results provide general insight into the biophysical transport mechanisms that may arise in viral attachment and entry.

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“…Moreover, the ability to attach functional biomolecules to the tip of the atomic force microscope has made it possible to characterise molecular recognition processes directly on the surfaces of living cells. This experimental approach has been widely applied to study cellular adhesion processes [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] and to map the distribution of membrane receptors, an application described in great details in several recent reviews [31][32][33][34].…”

Section: Introductionmentioning

confidence: 99%

AFM as a tool to probe and manipulate cellular processes

Lamontagne

Cuerrier

Grandbois

2007

Pflugers Arch - Eur J Physiol

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The exploration of molecular processes governing physiological functions has significantly benefited from the emergence of novel nanoscaled techniques. Atomic force microscopy in force measurement mode can be used to investigate a multitude of cellular events in individual living cells with great sensitivity. Precise regions of the plasma membrane can be examined in relation to particular signalling pathways activated by a mechanical stimulus. Similarly, subtle cellular movements induced by biochemical activation of specific membrane receptors can be detected in real time with excellent temporal and spatial resolution. The possibility to challenge locally and mechanically cell surface receptors also provides information on the control exerted by a cell over individual adhesion sites. Overall, this information is vital for an in-depth understanding of mechanisms related to cellular movement and morphological regulation. Lastly, atomic force microscope-based nanomanipulations on living cells have recently been proposed as a tool to influence and monitor cellular homeostasis by introducing specific molecular entities into or extracting them from the cytoplasm of individual cells. This review provides detailed examples on how such atomic force microscopy experiments can be conducted to investigate processes relevant to cell physiology.

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Single-Molecule Analysis of Human Immunodeficiency Virus Type 1 gp120-Receptor Interactions in Living Cells

Cited by 68 publications

References 44 publications

Influenza virus binds its host cell using multiple dynamic interactions

Influenza virus binds its host cell using multiple dynamic interactions

Diffusion-Dependent Mechanisms of Receptor Engagement and Viral Entry

AFM as a tool to probe and manipulate cellular processes

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