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

Pham, Son, Tabarin, Thibault, Garvey, Megan, Pade, Corinna, Rossy, Jeremie, Monaghan, Paul, Hyatt, Alex, Böcking, Till, Leis, Andrew, Gaus, Katharina and Mak, Johnson 2015, Cryo-electron microscopy and single molecule fluorescent microscopy detect CD4 receptor induced HIV size expansion prior to cell entry, Virology, vol. 486, pp. 121-133, doi: 10.1016/j.virol.2015.09.006.

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Title Cryo-electron microscopy and single molecule fluorescent microscopy detect CD4 receptor induced HIV size expansion prior to cell entry
Author(s) Pham, Son
Tabarin, Thibault
Garvey, Megan
Pade, Corinna
Rossy, Jeremie
Monaghan, Paul
Hyatt, Alex
Böcking, Till
Leis, Andrew
Gaus, Katharina
Mak, JohnsonORCID iD for Mak, Johnson orcid.org/0000-0002-5229-5707
Journal name Virology
Volume number 486
Start page 121
End page 133
Total pages 13
Publisher Elsevier
Place of publication Amsterdam, The Netherlands
Publication date 2015-12
ISSN 1096-0341
Keyword(s) Cryo-EM
Entry
HIV-1
Pre-entry priming
Retrovirus
Single molecule fluorescent imaging
Structural rearrangement
Super-resolution microscopy
Tomography
dSTORM
Summary 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.
Language eng
DOI 10.1016/j.virol.2015.09.006
Field of Research 110804 Medical Virology
Socio Economic Objective 920109 Infectious Diseases
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Grant ID NHMRC 1025273
Copyright notice ©2015, Elsevier
Persistent URL http://hdl.handle.net/10536/DRO/DU:30079530

Document type: Journal Article
Collection: School of Medicine
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Created: Fri, 13 Nov 2015, 13:04:51 EST

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