HIV-Envelope–Dependent Cell-Cell Fusion: Quantitative Studies

Interaction in vitro between cells infected with human immunodeficiency virus (HIV) and surrounding, uninfected, target cells often leads to cell fusion and the formation of multinucleated cells, called syncytia. The presence in HIV-infected individuals of virus strains able to induce syncytia in cu...

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Main Authors: Leonor Huerta, Nayali López-Balderas, Evelyn Rivera-Toledo, Guadalupe Sandoval, Guillermo Gómez-Icazbalceta, Carlos Villarreal, Edmundo Lamoyi, Carlos Larralde
Format: Article
Language:English
Published: Wiley 2009-01-01
Series:The Scientific World Journal
Online Access:http://dx.doi.org/10.1100/tsw.2009.90
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author Leonor Huerta
Nayali López-Balderas
Evelyn Rivera-Toledo
Guadalupe Sandoval
Guillermo Gómez-Icazbalceta
Carlos Villarreal
Edmundo Lamoyi
Carlos Larralde
author_facet Leonor Huerta
Nayali López-Balderas
Evelyn Rivera-Toledo
Guadalupe Sandoval
Guillermo Gómez-Icazbalceta
Carlos Villarreal
Edmundo Lamoyi
Carlos Larralde
author_sort Leonor Huerta
collection DOAJ
description Interaction in vitro between cells infected with human immunodeficiency virus (HIV) and surrounding, uninfected, target cells often leads to cell fusion and the formation of multinucleated cells, called syncytia. The presence in HIV-infected individuals of virus strains able to induce syncytia in cultures of T cells is associated with disease progression and AIDS. Even in the asymptomatic stage of infection, multinucleated cells have been observed in different organs, indicating that fused cells may be generated and remain viable in the tissues of patients. We used lymphocytic cells transfected for the expression of the HIV-envelope (Env) glycoproteins to develop a method for the direct quantification of fusion events by flow cytometry (Huerta et al., 2006, J. Virol. Methods 138, 17–23; López-Balderas et al., 2007, Virus Res. 123, 138–146). The method involves the staining of fusion partners with lipophilic probes and the use of fluorescence resonance energy transfer (FRET) to distinguish between fused and aggregated cells. We have shown that such a flow-cytometry assay is appropriate for the screening of compounds that have the potential to modulate HIV-Env–mediated cell fusion. Even those syncytia that are small or few in numbers can be detected. Quantitative analysis of the fusion products was performed with this technique; the results indicated that the time of reaction and initial proportion of fusion partners determine the number, relative size, and average cellular composition of syncytia. Heterogeneity of syncytia generated by HIV-Env–mediated cell-cell fusion may result in a variety of possible outcomes that, in turn, may influence the biological properties of the syncytia and surrounding cells, as well as replication of virus. Given the myriad immune abnormalities leading to AIDS, the full understanding of the extent, diverse composition, and role of fused cells in the pathogenesis of, and immune response to, HIV infection is an important, pending issue.
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spelling doaj-art-a7d74d88d3964ecb89d163237f68c1e42025-02-03T06:44:17ZengWileyThe Scientific World Journal1537-744X2009-01-01974676310.1100/tsw.2009.90HIV-Envelope–Dependent Cell-Cell Fusion: Quantitative StudiesLeonor Huerta0Nayali López-Balderas1Evelyn Rivera-Toledo2Guadalupe Sandoval3Guillermo Gómez-Icazbalceta4Carlos Villarreal5Edmundo Lamoyi6Carlos Larralde7Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Distrito Federal, CP 04510, MexicoDepartamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Distrito Federal, CP 04510, MexicoDepartamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Distrito Federal, CP 04510, MexicoDepartamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Distrito Federal, CP 04510, MexicoDepartamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Distrito Federal, CP 04510, MexicoDepartamento de Física Teórica, Instituto de Física, Universidad Nacional Autónoma de México, Ciudad Universitaria, Distrito Federal, CP 04510, MexicoDepartamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Distrito Federal, CP 04510, MexicoDepartamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Distrito Federal, CP 04510, MexicoInteraction in vitro between cells infected with human immunodeficiency virus (HIV) and surrounding, uninfected, target cells often leads to cell fusion and the formation of multinucleated cells, called syncytia. The presence in HIV-infected individuals of virus strains able to induce syncytia in cultures of T cells is associated with disease progression and AIDS. Even in the asymptomatic stage of infection, multinucleated cells have been observed in different organs, indicating that fused cells may be generated and remain viable in the tissues of patients. We used lymphocytic cells transfected for the expression of the HIV-envelope (Env) glycoproteins to develop a method for the direct quantification of fusion events by flow cytometry (Huerta et al., 2006, J. Virol. Methods 138, 17–23; López-Balderas et al., 2007, Virus Res. 123, 138–146). The method involves the staining of fusion partners with lipophilic probes and the use of fluorescence resonance energy transfer (FRET) to distinguish between fused and aggregated cells. We have shown that such a flow-cytometry assay is appropriate for the screening of compounds that have the potential to modulate HIV-Env–mediated cell fusion. Even those syncytia that are small or few in numbers can be detected. Quantitative analysis of the fusion products was performed with this technique; the results indicated that the time of reaction and initial proportion of fusion partners determine the number, relative size, and average cellular composition of syncytia. Heterogeneity of syncytia generated by HIV-Env–mediated cell-cell fusion may result in a variety of possible outcomes that, in turn, may influence the biological properties of the syncytia and surrounding cells, as well as replication of virus. Given the myriad immune abnormalities leading to AIDS, the full understanding of the extent, diverse composition, and role of fused cells in the pathogenesis of, and immune response to, HIV infection is an important, pending issue.http://dx.doi.org/10.1100/tsw.2009.90
spellingShingle Leonor Huerta
Nayali López-Balderas
Evelyn Rivera-Toledo
Guadalupe Sandoval
Guillermo Gómez-Icazbalceta
Carlos Villarreal
Edmundo Lamoyi
Carlos Larralde
HIV-Envelope–Dependent Cell-Cell Fusion: Quantitative Studies
The Scientific World Journal
title HIV-Envelope–Dependent Cell-Cell Fusion: Quantitative Studies
title_full HIV-Envelope–Dependent Cell-Cell Fusion: Quantitative Studies
title_fullStr HIV-Envelope–Dependent Cell-Cell Fusion: Quantitative Studies
title_full_unstemmed HIV-Envelope–Dependent Cell-Cell Fusion: Quantitative Studies
title_short HIV-Envelope–Dependent Cell-Cell Fusion: Quantitative Studies
title_sort hiv envelope dependent cell cell fusion quantitative studies
url http://dx.doi.org/10.1100/tsw.2009.90
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