HIV-1 envelope pseudotyped viral vectors and infectious molecular clones expressing the same envelope glycoprotein have a similar neutralization phenotype, but culture in peripheral blood mononuclear cells is associated with decreased neutralization sensitivity

Mark K. Louder; Anna Sambor; Elena Chertova; Tai Hunte; Sarah Barrett; Fallon Ojong; Eric Sanders-Buell; Susan Zolla-Pazner; Francine E. McCutchan; James D. Roser; Dana Gabuzda; Jeffrey D. Lifson; John R. Mascola

doi:10.1016/j.virol.2005.06.003

HIV-1 envelope pseudotyped viral vectors and infectious molecular clones expressing the same envelope glycoprotein have a similar neutralization phenotype, but culture in peripheral blood mononuclear cells is associated with decreased neutralization sensitivity

Mark K. Louder, Anna Sambor, Elena Chertova, Tai Hunte, Sarah Barrett, Fallon Ojong, Eric Sanders-Buell, Susan Zolla-Pazner, Francine E. McCutchan, James D. Roser, Dana Gabuzda, Jeffrey D. Lifson, John R. Mascola

Research output: Contribution to journal › Article › peer-review

88 Scopus citations

Abstract

Recombinant lentiviral vectors pseudotyped with heterologous HIV-1 envelope glycoproteins allow rapid and accurate measurement of antibody-mediated HIV-1 neutralization. However, the neutralization phenotypes of envelope pseudoviruses have not been directly compared to isogenic replication competent HIV-1. We produced pseudoviruses expressing three different HIV-1 envelope glycoproteins and subcloned the same three env genes into a replication competent NL4-3 molecular clone. For each of the antibodies tested, the neutralization dose-response curves of pseudoviruses and corresponding replication competent viruses were similar. Thus, envelope pseudoviruses can be used to study the anti-HIV-1 neutralizing antibody response. A single passage of replication competent virus derived from 293T cells through peripheral blood mononuclear cells (PBMC) caused a substantial decrease in sensitivity to neutralizing antibodies. This was associated with an increase in average virion envelope glycoprotein content of the PBMC-derived virus. Replication competent HIV-1 and isogenic envelope pseudoviruses have similar neutralization characteristics, but passage into PBMC is associated with decreased sensitivity to neutralization.

Original language	English
Pages (from-to)	226-238
Number of pages	13
Journal	Virology
Volume	339
Issue number	2
DOIs	https://doi.org/10.1016/j.virol.2005.06.003
State	Published - 1 Sep 2005
Externally published	Yes

Keywords

HIV-1
Neutralizing antibodies
Pseudovirus
Vaccines

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10.1016/j.virol.2005.06.003

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Louder, M. K., Sambor, A., Chertova, E., Hunte, T., Barrett, S., Ojong, F., Sanders-Buell, E., Zolla-Pazner, S., McCutchan, F. E., Roser, J. D., Gabuzda, D., Lifson, J. D., & Mascola, J. R. (2005). HIV-1 envelope pseudotyped viral vectors and infectious molecular clones expressing the same envelope glycoprotein have a similar neutralization phenotype, but culture in peripheral blood mononuclear cells is associated with decreased neutralization sensitivity. Virology, 339(2), 226-238. https://doi.org/10.1016/j.virol.2005.06.003

Louder, Mark K. ; Sambor, Anna ; Chertova, Elena et al. / HIV-1 envelope pseudotyped viral vectors and infectious molecular clones expressing the same envelope glycoprotein have a similar neutralization phenotype, but culture in peripheral blood mononuclear cells is associated with decreased neutralization sensitivity. In: Virology. 2005 ; Vol. 339, No. 2. pp. 226-238.

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title = "HIV-1 envelope pseudotyped viral vectors and infectious molecular clones expressing the same envelope glycoprotein have a similar neutralization phenotype, but culture in peripheral blood mononuclear cells is associated with decreased neutralization sensitivity",

abstract = "Recombinant lentiviral vectors pseudotyped with heterologous HIV-1 envelope glycoproteins allow rapid and accurate measurement of antibody-mediated HIV-1 neutralization. However, the neutralization phenotypes of envelope pseudoviruses have not been directly compared to isogenic replication competent HIV-1. We produced pseudoviruses expressing three different HIV-1 envelope glycoproteins and subcloned the same three env genes into a replication competent NL4-3 molecular clone. For each of the antibodies tested, the neutralization dose-response curves of pseudoviruses and corresponding replication competent viruses were similar. Thus, envelope pseudoviruses can be used to study the anti-HIV-1 neutralizing antibody response. A single passage of replication competent virus derived from 293T cells through peripheral blood mononuclear cells (PBMC) caused a substantial decrease in sensitivity to neutralizing antibodies. This was associated with an increase in average virion envelope glycoprotein content of the PBMC-derived virus. Replication competent HIV-1 and isogenic envelope pseudoviruses have similar neutralization characteristics, but passage into PBMC is associated with decreased sensitivity to neutralization.",

keywords = "HIV-1, Neutralizing antibodies, Pseudovirus, Vaccines",

author = "Louder, \{Mark K.\} and Anna Sambor and Elena Chertova and Tai Hunte and Sarah Barrett and Fallon Ojong and Eric Sanders-Buell and Susan Zolla-Pazner and McCutchan, \{Francine E.\} and Roser, \{James D.\} and Dana Gabuzda and Lifson, \{Jeffrey D.\} and Mascola, \{John R.\}",

note = "Funding Information: We thank Hermann Katinger and Gabriela Stiegler for providing mAbs 2F5, 4E10 and 2G12 and Dennis Burton for contributing mAb b12. We appreciate the excellent technical contributions of David Ott, Sarah Winfrey, Krisha Svehla and Brent Welcher. We thank David Montefiori, Rich Wyatt and Sanjay Phogat for helpful discussions and Brenda Hartman for graphics assistance. This work was supported in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. NO1-CO-124000. D.G. was supported by NS37277. ",

year = "2005",

month = sep,

day = "1",

doi = "10.1016/j.virol.2005.06.003",

language = "English",

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Louder, MK, Sambor, A, Chertova, E, Hunte, T, Barrett, S, Ojong, F, Sanders-Buell, E, Zolla-Pazner, S, McCutchan, FE, Roser, JD, Gabuzda, D, Lifson, JD & Mascola, JR 2005, 'HIV-1 envelope pseudotyped viral vectors and infectious molecular clones expressing the same envelope glycoprotein have a similar neutralization phenotype, but culture in peripheral blood mononuclear cells is associated with decreased neutralization sensitivity', Virology, vol. 339, no. 2, pp. 226-238. https://doi.org/10.1016/j.virol.2005.06.003

HIV-1 envelope pseudotyped viral vectors and infectious molecular clones expressing the same envelope glycoprotein have a similar neutralization phenotype, but culture in peripheral blood mononuclear cells is associated with decreased neutralization sensitivity. / Louder, Mark K.; Sambor, Anna; Chertova, Elena et al.
In: Virology, Vol. 339, No. 2, 01.09.2005, p. 226-238.

Research output: Contribution to journal › Article › peer-review

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AU - Louder, Mark K.

AU - Sambor, Anna

AU - Chertova, Elena

AU - Hunte, Tai

AU - Barrett, Sarah

AU - Ojong, Fallon

AU - Sanders-Buell, Eric

AU - Zolla-Pazner, Susan

AU - McCutchan, Francine E.

AU - Roser, James D.

AU - Gabuzda, Dana

AU - Lifson, Jeffrey D.

AU - Mascola, John R.

N1 - Funding Information: We thank Hermann Katinger and Gabriela Stiegler for providing mAbs 2F5, 4E10 and 2G12 and Dennis Burton for contributing mAb b12. We appreciate the excellent technical contributions of David Ott, Sarah Winfrey, Krisha Svehla and Brent Welcher. We thank David Montefiori, Rich Wyatt and Sanjay Phogat for helpful discussions and Brenda Hartman for graphics assistance. This work was supported in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. NO1-CO-124000. D.G. was supported by NS37277.

PY - 2005/9/1

Y1 - 2005/9/1

N2 - Recombinant lentiviral vectors pseudotyped with heterologous HIV-1 envelope glycoproteins allow rapid and accurate measurement of antibody-mediated HIV-1 neutralization. However, the neutralization phenotypes of envelope pseudoviruses have not been directly compared to isogenic replication competent HIV-1. We produced pseudoviruses expressing three different HIV-1 envelope glycoproteins and subcloned the same three env genes into a replication competent NL4-3 molecular clone. For each of the antibodies tested, the neutralization dose-response curves of pseudoviruses and corresponding replication competent viruses were similar. Thus, envelope pseudoviruses can be used to study the anti-HIV-1 neutralizing antibody response. A single passage of replication competent virus derived from 293T cells through peripheral blood mononuclear cells (PBMC) caused a substantial decrease in sensitivity to neutralizing antibodies. This was associated with an increase in average virion envelope glycoprotein content of the PBMC-derived virus. Replication competent HIV-1 and isogenic envelope pseudoviruses have similar neutralization characteristics, but passage into PBMC is associated with decreased sensitivity to neutralization.

AB - Recombinant lentiviral vectors pseudotyped with heterologous HIV-1 envelope glycoproteins allow rapid and accurate measurement of antibody-mediated HIV-1 neutralization. However, the neutralization phenotypes of envelope pseudoviruses have not been directly compared to isogenic replication competent HIV-1. We produced pseudoviruses expressing three different HIV-1 envelope glycoproteins and subcloned the same three env genes into a replication competent NL4-3 molecular clone. For each of the antibodies tested, the neutralization dose-response curves of pseudoviruses and corresponding replication competent viruses were similar. Thus, envelope pseudoviruses can be used to study the anti-HIV-1 neutralizing antibody response. A single passage of replication competent virus derived from 293T cells through peripheral blood mononuclear cells (PBMC) caused a substantial decrease in sensitivity to neutralizing antibodies. This was associated with an increase in average virion envelope glycoprotein content of the PBMC-derived virus. Replication competent HIV-1 and isogenic envelope pseudoviruses have similar neutralization characteristics, but passage into PBMC is associated with decreased sensitivity to neutralization.

KW - HIV-1

KW - Neutralizing antibodies

KW - Pseudovirus

KW - Vaccines

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Louder MK, Sambor A, Chertova E, Hunte T, Barrett S, Ojong F et al. HIV-1 envelope pseudotyped viral vectors and infectious molecular clones expressing the same envelope glycoprotein have a similar neutralization phenotype, but culture in peripheral blood mononuclear cells is associated with decreased neutralization sensitivity. Virology. 2005 Sep 1;339(2):226-238. doi: 10.1016/j.virol.2005.06.003