Single-molecule super-resolution imaging of T-cell plasma membrane CD4 redistribution upon HIV-1 binding. Yuan, Y., Jacobs, C. A, Garcia, I. L., Pereira, P. M, Lawrence, S. P, Laine, R. F, Marsh, M., Henriques, R., & Risco, C. Viruses, 13(1):142, 2021.
Paper doi abstract bibtex Citation: Yuan, Y.; Jacobs, C.A.; Llorente Garcia, I.; Pereira, P.M.; Lawrence, S.P.; Laine, R.F.; Marsh, M.; Henriques, R. Single-Molecule Super-Resolution Imaging of T-Cell Plasma Membrane CD4 Redistribution upon HIV-1 Binding. Viruses 2021, 13, 142. Abstract: The first step of cellular entry for the human immunodeficiency virus type-1 (HIV-1) occurs through the binding of its envelope protein (Env) with the plasma membrane receptor CD4 and co-receptor CCR5 or CXCR4 on susceptible cells, primarily CD4 + T cells and macrophages. Although there is considerable knowledge of the molecular interactions between Env and host cell receptors that lead to successful fusion, the precise way in which HIV-1 receptors redistribute to sites of virus binding at the nanoscale remains unknown. Here, we quantitatively examine changes in the nanoscale organisation of CD4 on the surface of CD4 + T cells following HIV-1 binding. Using single-molecule super-resolution imaging, we show that CD4 molecules are distributed mostly as either individual molecules or small clusters of up to 4 molecules. Following virus binding, we observe a local 3-to-10-fold increase in cluster diameter and molecule number for virus-associated CD4 clusters. Moreover, a similar but smaller magnitude reorganisation of CD4 was also observed with recombinant gp120. For one of the first times, our results quantify the nanoscale CD4 reorganisation triggered by HIV-1 on host CD4 + T cells. Our quantitative approach provides a robust methodology for characterising the nanoscale organisation of plasma membrane receptors in general with the potential to link spatial organisation to function.
@article{Yuan2021,
abstract = {Citation: Yuan, Y.; Jacobs, C.A.; Llorente Garcia, I.; Pereira, P.M.; Lawrence, S.P.; Laine, R.F.; Marsh, M.; Henriques, R. Single-Molecule Super-Resolution Imaging of T-Cell Plasma Membrane CD4 Redistribution upon HIV-1 Binding. Viruses 2021, 13, 142. Abstract: The first step of cellular entry for the human immunodeficiency virus type-1 (HIV-1) occurs through the binding of its envelope protein (Env) with the plasma membrane receptor CD4 and co-receptor CCR5 or CXCR4 on susceptible cells, primarily CD4 + T cells and macrophages. Although there is considerable knowledge of the molecular interactions between Env and host cell receptors that lead to successful fusion, the precise way in which HIV-1 receptors redistribute to sites of virus binding at the nanoscale remains unknown. Here, we quantitatively examine changes in the nanoscale organisation of CD4 on the surface of CD4 + T cells following HIV-1 binding. Using single-molecule super-resolution imaging, we show that CD4 molecules are distributed mostly as either individual molecules or small clusters of up to 4 molecules. Following virus binding, we observe a local 3-to-10-fold increase in cluster diameter and molecule number for virus-associated CD4 clusters. Moreover, a similar but smaller magnitude reorganisation of CD4 was also observed with recombinant gp120. For one of the first times, our results quantify the nanoscale CD4 reorganisation triggered by HIV-1 on host CD4 + T cells. Our quantitative approach provides a robust methodology for characterising the nanoscale organisation of plasma membrane receptors in general with the potential to link spatial organisation to function.},
author = {Yuan, Yue and Jacobs, Caron A and Garcia, Isabel Llorente and Pereira, Pedro M and Lawrence, Scott P and Laine, Romain F and Marsh, Mark and Henriques, Ricardo and Risco, Cristina},
doi = {10.3390/v13010142},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Yuan et al. - 2021 - Single-molecule super-resolution imaging of T-cell plasma membrane CD4 redistribution upon HIV-1 binding.pdf:pdf},
journal = {Viruses},
keywords = {CD4,HIV-1entry,OA,STORM,fund{\_}ack,modelling,nanoscalecluster,original,quantitativeanalysis,super-resolutionmicroscopy,viralreceptor},
mendeley-tags = {OA,fund{\_}ack,original},
number = {1},
pages = {142},
pmid = {33478139},
title = {{Single-molecule super-resolution imaging of T-cell plasma membrane CD4 redistribution upon HIV-1 binding}},
url = {https://doi.org/10.3390/v13010142},
volume = {13},
year = {2021}
}
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