Imperial College London
Alternate

ProfessorRobinShattock

Faculty of Medicine, Department of Infectious Disease

Chair in Mucosal Infection and Immunity
 
 
 
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Contact

 

+44 (0)20 7594 5206r.shattock

 
 
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Location

 

453Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Stieh:2013:10.1186/1742-4690-10-33,
author = {Stieh, DJ and Phillips, JL and Rogers, PM and King, DF and Cianci, GC and Jeffs, SA and Gnanakaran, S and Shattock, RJ},
doi = {10.1186/1742-4690-10-33},
journal = {Retrovirology},
title = {Dynamic electrophoretic fingerprinting of the HIV-1 envelope glycoprotein},
url = {http://dx.doi.org/10.1186/1742-4690-10-33},
volume = {10},
year = {2013}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background: Interactions between the HIV-1 envelope glycoprotein (Env) and its primary receptor CD4 areinfluenced by the physiological setting in which these events take place. In this study, we explored the surfacechemistry of HIV-1 Env constructs at a range of pH and salinities relevant to mucosal and systemic compartmentsthrough electrophoretic mobility (EM) measurements. Sexual transmission events provide a more acidicenvironment for HIV-1 compared to dissemination and spread of infection occurring in blood or lymph node. Wehypothesize functional, trimeric Env behaves differently than monomeric forms.Results: The dynamic electrophoretic fingerprint of trimeric gp140 revealed a change in EM from strongly negativeto strongly positive as pH increased from that of the lower female genital tract (pHx) to that of the blood (pHy).Similar findings were observed using a trimeric influenza Haemagglutinin (HA) glycoprotein, indicating that thismay be a general attribute of trimeric viral envelope glycoproteins. These findings were supported bycomputationally modeling the surface charge of various gp120 and HA crystal structures. To identify the behaviorof the infectious agent and its target cells, EM measurements were made on purified whole HIV-1 virions andprimary T-lymphocytes. Viral particles had a largely negative surface charge, and lacked the regions of positivitynear neutral pH that were observed with trimeric Env. T cells changed their surface chemistry as a function ofactivation state, becoming more negative over a wider range of pH after activation. Soluble recombinant CD4(sCD4) was found to be positively charged under a wide range of conditions. Binding studies between sCD4 andgp140 show that the affinity of CD4-gp140 interactions depends on pH.Conclusions: Taken together, these findings allow a more complete model of the electrochemical forces involvedin HIV-1 Env functionality. These results indicate that the influence of the localized environment on the inter
AU  - Stieh,DJ
AU  - Phillips,JL
AU  - Rogers,PM
AU  - King,DF
AU  - Cianci,GC
AU  - Jeffs,SA
AU  - Gnanakaran,S
AU  - Shattock,RJ
DO  - 10.1186/1742-4690-10-33
PY  - 2013///
SN  - 1742-4690
TI  - Dynamic electrophoretic fingerprinting of the HIV-1 envelope glycoprotein
T2  - Retrovirology
UR  - http://dx.doi.org/10.1186/1742-4690-10-33
UR  - http://hdl.handle.net/10044/1/28663
VL  - 10
ER  -
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