Single-molecule super-resolution imaging of t-cell plasma membrane cd4 redistribution upon hiv-1 binding

Yue Yuan, Caron A. Jacobs, Isabel Llorente Garcia, Pedro M. Pereira, Scott P. Lawrence, Romain F. Laine, Mark Marsh, Ricardo Henriques

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

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.

Original languageEnglish
Article number142
JournalViruses
Volume13
Issue number1
DOIs
Publication statusPublished - Jan 2021

Keywords

  • CD4
  • HIV-1 entry
  • Modelling
  • Nanoscale cluster
  • Quantitative analysis
  • STORM
  • Super-resolution microscopy
  • Viral receptor

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