Imperial College London
Alternate

Emeritus ProfessorMyraMcClure

Faculty of Medicine, Department of Infectious Disease

Emeritus Professor of Retrovirology
 
 
 
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Contact

 

+44 (0)20 7594 3902m.mcclure

 
 
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Location

 

456Medical SchoolSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lai:2011:10.1371/journal.ppat.1002442,
author = {Lai, RPJ and Yan, J and Heeney, J and McClure, MO and Goettlinger, H and Luban, J and Pizzato, M},
doi = {10.1371/journal.ppat.1002442},
journal = {PLOS PATHOGENS},
title = {Nef Decreases HIV-1 Sensitivity to Neutralizing Antibodies that Target the Membrane-proximal External Region of TMgp41},
url = {http://dx.doi.org/10.1371/journal.ppat.1002442},
volume = {7},
year = {2011}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Primate lentivirus nef is required for sustained virus replication in vivo and accelerated progression to AIDS. While exploring the mechanism by which Nef increases the infectivity of cell-free virions, we investigated a functional link between Nef and Env. Since we failed to detect an effect of Nef on the quantity of virion-associated Env, we searched for qualitative changes by examining whether Nef alters HIV-1 sensitivity to agents that target distinct features of Env. Nef conferred as much as 50-fold resistance to 2F5 and 4E10, two potent neutralizing monoclonal antibodies (nAbs) that target the membrane proximal external region (MPER) of TMgp41. In contrast, Nef had no effect on HIV-1 neutralization by MPER-specific nAb Z13e1, by the peptide inhibitor T20, nor by a panel of nAbs and other reagents targeting gp120. Resistance to neutralization by 2F5 and 4E10 was observed with Nef from a diverse range of HIV-1 and SIV isolates, as well as with HIV-1 virions bearing Env from CCR5- and CXCR4-tropic viruses, clade B and C viruses, or primary isolates. Functional analysis of a panel of Nef mutants revealed that this activity requires Nef myristoylation but that it is genetically separable from other Nef functions such as the ability to enhance virus infectivity and to downregulate CD4. Glycosylated-Gag from MoMLV substituted for Nef in conferring resistance to 2F5 and 4E10, indicating that this activity is conserved in a retrovirus that does not encode Nef. Given the reported membrane-dependence of MPER-recognition by 2F5 and 4E10, in contrast to the membrane-independence of Z13e1, the data here is consistent with a model in which Nef alters MPER recognition in the context of the virion membrane. Indeed, Nef and Glycosylated-Gag decreased the efficiency of virion capture by 2F5 and 4E10, but not by other nAbs. These studies demonstrate that Nef protects lentiviruses from one of the most broadly-acting classes of neutralizing antibodies. This newly discovered activit
AU  - Lai,RPJ
AU  - Yan,J
AU  - Heeney,J
AU  - McClure,MO
AU  - Goettlinger,H
AU  - Luban,J
AU  - Pizzato,M
DO  - 10.1371/journal.ppat.1002442
PY  - 2011///
SN  - 1553-7366
TI  - Nef Decreases HIV-1 Sensitivity to Neutralizing Antibodies that Target the Membrane-proximal External Region of TMgp41
T2  - PLOS PATHOGENS
UR  - http://dx.doi.org/10.1371/journal.ppat.1002442
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000299108500051&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/62233
VL  - 7
ER  -
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