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Journal of Virology, August 2009, p. 7883-7893, Vol. 83, No. 16
0022-538X/09/$08.00+0     doi:10.1128/JVI.00582-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Introduction of Exogenous Epitopes in the Variable Regions of the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein: Effect on Viral Infectivity and the Neutralization Phenotype{triangledown}

Aaron Wallace1 and Leonidas Stamatatos1,2*

Seattle Biomedical Research Institute,1 Department of Global Health, University of Washington, Seattle, Washington 981092

Received 20 March 2009/ Accepted 27 May 2009

In this study we examined whether human immunodeficiency virus type 1 (HIV-1) is equally susceptible to neutralization by a given antibody when the epitope of this antibody is introduced at different positions within the viral envelope glycoprotein (Env). To this end, we introduced two exogenous "epitope tags" at different locations within three major Env regions in two distinct HIV-1 isolates. We examined how the introduction of the exogenous epitopes affects Env expression, Env incorporation into virions, Env fusogenic potential, and viral susceptibility to neutralization. Our data indicate that even within the same Env region, the exact positioning of the epitope impacts the susceptibility of the virus to neutralization by the antibody that binds to that epitope. Our data also indicate that even if the same epitope is introduced in the exact same position on two different Envs, its exposure and, as a result, the neutralization susceptibility of the virus, can be very different. In contrast to the findings of previous studies conducted with HIV-1 isolates other than those used here, but in agreement with results obtained with simian immunodeficiency virus, we observed that tagging of the fourth variable region of Env (V4) did not result in neutralization by the anti-tag antibodies. Our data indicate that epitopes in V4 are not properly exposed within the functional HIV-1 trimeric Env spike, suggesting that V4 may not be a good target for vaccine-elicited neutralizing antibodies.

* Corresponding author. Mailing address: Seattle Biomedical Research Institute, 307 Westlake Avenue North, Seattle, WA 98109. Phone: (206) 256-7200. Fax: (206) 256-7229. E-mail: leo.stamatatos{at}sbri.org

{triangledown} Published ahead of print on 3 June 2009.

Journal of Virology, August 2009, p. 7883-7893, Vol. 83, No. 16
0022-538X/09/$08.00+0     doi:10.1128/JVI.00582-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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