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Title: Incorporation of chimeric HIV-SIV-Env and modified HIV-Env proteins into HIV pseudovirions

Abstract

Low level incorporation of the viral glycoprotein (Env) into human immunodeficiency virus (HIV) particles is a major drawback for vaccine strategies against HIV/AIDS in which HIV particles are used as immunogen. Within this study, we have examined two strategies aimed at achieving higher levels of Env incorporation into non-infectious pseudovirions (PVs). First, we have generated chimeric HIV/SIV Env proteins containing the truncated C-terminal tail region of simian immunodeficiency virus (SIV)mac239-Env767{sup stop}, which mediates strongly increased incorporation of SIV-Env into SIV particles. In a second strategy, we have employed a truncated HIV-Env protein (Env-Tr752{sup N750K}) which we have previously demonstrated to be incorporated into HIV virions, generated in infected T-cells, to a higher level than that of Wt-HIV-Env. Although the chimeric HIV/SIV Env proteins were expressed at the cell surface and induced increased levels of cell-cell fusion in comparison to Wt-HIV-Env, they did not exhibit increased incorporation into either HIV-PVs or SIV-PVs. Only Env-Tr752{sup N750K} exhibited significantly higher (threefold) levels of incorporation into HIV-PVs, an improvement, which, although not dramatic, is worthwhile for the large-scale preparation of non-infectious PVs for vaccine studies aimed at inducing Env humoral responses.

Authors:
 [1];  [1];  [1];  [1];  [1];  [2]
  1. Forschungsschwerpunkt Infektion und Krebs, F020, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120 Heidelberg (Germany)
  2. Forschungsschwerpunkt Infektion und Krebs, F020, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120 Heidelberg (Germany). E-mail: v.bosch@dkfz.de
Publication Date:
OSTI Identifier:
20977023
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 361; Journal Issue: 2; Other Information: DOI: 10.1016/j.virol.2006.11.029; PII: S0042-6822(06)00878-6; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AIDS; AIDS VIRUS; BIOTECHNOLOGY; GLYCOPROTEINS; HUMAN POPULATIONS; VACCINES

Citation Formats

Devitt, Gerard, Emerson, Vanessa, Holtkotte, Denise, Pfeiffer, Tanya, Pisch, Thorsten, and Bosch, Valerie. Incorporation of chimeric HIV-SIV-Env and modified HIV-Env proteins into HIV pseudovirions. United States: N. p., 2007. Web. doi:10.1016/j.virol.2006.11.029.
Devitt, Gerard, Emerson, Vanessa, Holtkotte, Denise, Pfeiffer, Tanya, Pisch, Thorsten, & Bosch, Valerie. Incorporation of chimeric HIV-SIV-Env and modified HIV-Env proteins into HIV pseudovirions. United States. doi:10.1016/j.virol.2006.11.029.
Devitt, Gerard, Emerson, Vanessa, Holtkotte, Denise, Pfeiffer, Tanya, Pisch, Thorsten, and Bosch, Valerie. Thu . "Incorporation of chimeric HIV-SIV-Env and modified HIV-Env proteins into HIV pseudovirions". United States. doi:10.1016/j.virol.2006.11.029.
@article{osti_20977023,
title = {Incorporation of chimeric HIV-SIV-Env and modified HIV-Env proteins into HIV pseudovirions},
author = {Devitt, Gerard and Emerson, Vanessa and Holtkotte, Denise and Pfeiffer, Tanya and Pisch, Thorsten and Bosch, Valerie},
abstractNote = {Low level incorporation of the viral glycoprotein (Env) into human immunodeficiency virus (HIV) particles is a major drawback for vaccine strategies against HIV/AIDS in which HIV particles are used as immunogen. Within this study, we have examined two strategies aimed at achieving higher levels of Env incorporation into non-infectious pseudovirions (PVs). First, we have generated chimeric HIV/SIV Env proteins containing the truncated C-terminal tail region of simian immunodeficiency virus (SIV)mac239-Env767{sup stop}, which mediates strongly increased incorporation of SIV-Env into SIV particles. In a second strategy, we have employed a truncated HIV-Env protein (Env-Tr752{sup N750K}) which we have previously demonstrated to be incorporated into HIV virions, generated in infected T-cells, to a higher level than that of Wt-HIV-Env. Although the chimeric HIV/SIV Env proteins were expressed at the cell surface and induced increased levels of cell-cell fusion in comparison to Wt-HIV-Env, they did not exhibit increased incorporation into either HIV-PVs or SIV-PVs. Only Env-Tr752{sup N750K} exhibited significantly higher (threefold) levels of incorporation into HIV-PVs, an improvement, which, although not dramatic, is worthwhile for the large-scale preparation of non-infectious PVs for vaccine studies aimed at inducing Env humoral responses.},
doi = {10.1016/j.virol.2006.11.029},
journal = {Virology},
number = 2,
volume = 361,
place = {United States},
year = {Thu May 10 00:00:00 EDT 2007},
month = {Thu May 10 00:00:00 EDT 2007}
}