Elsevier

Virology

Volume 486, December 2015, Pages 121-133
Virology

Cryo-electron microscopy and single molecule fluorescent microscopy detect CD4 receptor induced HIV size expansion prior to cell entry

https://doi.org/10.1016/j.virol.2015.09.006Get rights and content
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Highlights

  • Cell free viruses are able to receive external trigger that leads to apparent size expansion.

  • Virus envelope and CD4 receptor engagement is the lynchpin of virus size expansion.

  • Internal capsid organisation can influence receptor mediated virus size expansion.

  • Pre-existing virus-associated lipid membrane in cell free virus can accommodate the receptor mediated virus size expansion.

Abstract

Viruses are often thought to have static structure, and they only remodel after the viruses have entered target cells. Here, we detected a size expansion of virus particles prior to viral entry using cryo-electron microscopy (cryo-EM) and single molecule fluorescence imaging. HIV expanded both under cell-free conditions with soluble receptor CD4 (sCD4) targeting the CD4 binding site on the HIV-1 envelope protein (Env) and when HIV binds to receptor on cellular membrane. We have shown that the HIV Env is needed to facilitate receptor induced virus size expansions, showing that the ‘lynchpin’ for size expansion is highly specific. We demonstrate that the size expansion required maturation of HIV and an internal capsid core with wild type stability, suggesting that different HIV compartments are linked and are involved in remodelling. Our work reveals a previously unknown event in HIV entry, and we propose that this pre-entry priming process enables HIV particles to facilitate the subsequent steps in infection.

Keywords

HIV-1
Retrovirus
Entry
Structural rearrangement
Pre-entry priming
Cryo-EM
dSTORM
Super-resolution microscopy
Tomography
Single molecule fluorescent imaging

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1

These authors contributed equally to this work.