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

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2015
Autor:innen
Pham, Son
Tabarin, Thibault
Garvey, Megan
Pade, Corinna
Monaghan, Paul
Hyatt, Alex
Böcking, Till
Gaus, Katharina
Mak, Johnson
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Virology. 2015, 486, pp. 121-133. ISSN 0042-6822. eISSN 1096-0341. Available under: doi: 10.1016/j.virol.2015.09.006
Zusammenfassung

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.

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Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
HIV-1, Retrovirus, Entry, Structural rearrangement, Pre-entry priming, Cryo-EM, dSTORM, Super-resolution microscopy, Tomography, Single molecule fluorescent imaging
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ISO 690PHAM, Son, Thibault TABARIN, Megan GARVEY, Corinna PADE, Jérémie ROSSY, Paul MONAGHAN, Alex HYATT, Till BÖCKING, Katharina GAUS, Johnson MAK, 2015. Cryo-electron microscopy and single molecule fluorescent microscopy detect CD4 receptor induced HIV size expansion prior to cell entry. In: Virology. 2015, 486, pp. 121-133. ISSN 0042-6822. eISSN 1096-0341. Available under: doi: 10.1016/j.virol.2015.09.006
BibTex
@article{Pham2015Cryoe-42987,
  year={2015},
  doi={10.1016/j.virol.2015.09.006},
  title={Cryo-electron microscopy and single molecule fluorescent microscopy detect CD4 receptor induced HIV size expansion prior to cell entry},
  volume={486},
  issn={0042-6822},
  journal={Virology},
  pages={121--133},
  author={Pham, Son and Tabarin, Thibault and Garvey, Megan and Pade, Corinna and Rossy, Jérémie and Monaghan, Paul and Hyatt, Alex and Böcking, Till and Gaus, Katharina and Mak, Johnson}
}
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