Identification of Vimentin as a Potential Therapeutic Target against HIV Infection

A combination of antiviral drugs known as antiretroviral therapy (ART) has shown effectiveness against the human immunodeficiency virus (HIV). ART has markedly decreased mortality and morbidity among HIV-infected patients, having even reduced HIV transmission. However, an important current disadvant...

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Main Authors: Celia Fernández-Ortega, Anna Ramírez, Dionne Casillas, Taimi Paneque, Raimundo Ubieta, Marta Dubed, Leonor Navea, Lila Castellanos-Serra, Carlos Duarte, Viviana Falcon, Osvaldo Reyes, Hilda Garay, Eladio Silva, Enrique Noa, Yassel Ramos, Vladimir Besada, Lázaro Betancourt
Format: Article
Language:English
Published: MDPI AG 2016-06-01
Series:Viruses
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Online Access:http://www.mdpi.com/1999-4915/8/6/98
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author Celia Fernández-Ortega
Anna Ramírez
Dionne Casillas
Taimi Paneque
Raimundo Ubieta
Marta Dubed
Leonor Navea
Lila Castellanos-Serra
Carlos Duarte
Viviana Falcon
Osvaldo Reyes
Hilda Garay
Eladio Silva
Enrique Noa
Yassel Ramos
Vladimir Besada
Lázaro Betancourt
author_facet Celia Fernández-Ortega
Anna Ramírez
Dionne Casillas
Taimi Paneque
Raimundo Ubieta
Marta Dubed
Leonor Navea
Lila Castellanos-Serra
Carlos Duarte
Viviana Falcon
Osvaldo Reyes
Hilda Garay
Eladio Silva
Enrique Noa
Yassel Ramos
Vladimir Besada
Lázaro Betancourt
author_sort Celia Fernández-Ortega
collection DOAJ
description A combination of antiviral drugs known as antiretroviral therapy (ART) has shown effectiveness against the human immunodeficiency virus (HIV). ART has markedly decreased mortality and morbidity among HIV-infected patients, having even reduced HIV transmission. However, an important current disadvantage, resistance development, remains to be solved. Hope is focused on developing drugs against cellular targets. This strategy is expected to prevent the emergence of viral resistance. In this study, using a comparative proteomic approach in MT4 cells treated with an anti-HIV leukocyte extract, we identified vimentin, a molecule forming intermediate filaments in the cell, as a possible target against HIV infection. We demonstrated a strong reduction of an HIV-1 based lentivirus expressing the enhanced green fluorescent protein (eGFP) in vimentin knockdown cells, and a noteworthy decrease of HIV-1 capsid protein antigen (CAp24) in those cells using a multiround infectivity assay. Electron micrographs showed changes in the structure of intermediate filaments when MT4 cells were treated with an anti-HIV leukocyte extract. Changes in the structure of intermediate filaments were also observed in vimentin knockdown MT4 cells. A synthetic peptide derived from a cytoskeleton protein showed potent inhibitory activity on HIV-1 infection, and low cytotoxicity. Our data suggest that vimentin can be a suitable target to inhibit HIV-1.
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spelling doaj.art-c5cc3b38b55a492399329cb042f505642022-12-22T02:31:29ZengMDPI AGViruses1999-49152016-06-01869810.3390/v8060098v8060098Identification of Vimentin as a Potential Therapeutic Target against HIV InfectionCelia Fernández-Ortega0Anna Ramírez1Dionne Casillas2Taimi Paneque3Raimundo Ubieta4Marta Dubed5Leonor Navea6Lila Castellanos-Serra7Carlos Duarte8Viviana Falcon9Osvaldo Reyes10Hilda Garay11Eladio Silva12Enrique Noa13Yassel Ramos14Vladimir Besada15Lázaro Betancourt16Center for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanacán, Playa, P.O. Box 6162, Havana 10600, CubaCenter for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanacán, Playa, P.O. Box 6162, Havana 10600, CubaCenter for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanacán, Playa, P.O. Box 6162, Havana 10600, CubaCenter for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanacán, Playa, P.O. Box 6162, Havana 10600, CubaCenter for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanacán, Playa, P.O. Box 6162, Havana 10600, CubaLaboratory for AIDS Research, Carretera de Tapaste y Autopista Nacional, San José de las Lajas, Mayabeque CP 32700, CubaLaboratory for AIDS Research, Carretera de Tapaste y Autopista Nacional, San José de las Lajas, Mayabeque CP 32700, CubaCenter for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanacán, Playa, P.O. Box 6162, Havana 10600, CubaCenter for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanacán, Playa, P.O. Box 6162, Havana 10600, CubaCenter for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanacán, Playa, P.O. Box 6162, Havana 10600, CubaCenter for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanacán, Playa, P.O. Box 6162, Havana 10600, CubaCenter for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanacán, Playa, P.O. Box 6162, Havana 10600, CubaLaboratory for AIDS Research, Carretera de Tapaste y Autopista Nacional, San José de las Lajas, Mayabeque CP 32700, CubaLaboratory for AIDS Research, Carretera de Tapaste y Autopista Nacional, San José de las Lajas, Mayabeque CP 32700, CubaCenter for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanacán, Playa, P.O. Box 6162, Havana 10600, CubaCenter for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanacán, Playa, P.O. Box 6162, Havana 10600, CubaCenter for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanacán, Playa, P.O. Box 6162, Havana 10600, CubaA combination of antiviral drugs known as antiretroviral therapy (ART) has shown effectiveness against the human immunodeficiency virus (HIV). ART has markedly decreased mortality and morbidity among HIV-infected patients, having even reduced HIV transmission. However, an important current disadvantage, resistance development, remains to be solved. Hope is focused on developing drugs against cellular targets. This strategy is expected to prevent the emergence of viral resistance. In this study, using a comparative proteomic approach in MT4 cells treated with an anti-HIV leukocyte extract, we identified vimentin, a molecule forming intermediate filaments in the cell, as a possible target against HIV infection. We demonstrated a strong reduction of an HIV-1 based lentivirus expressing the enhanced green fluorescent protein (eGFP) in vimentin knockdown cells, and a noteworthy decrease of HIV-1 capsid protein antigen (CAp24) in those cells using a multiround infectivity assay. Electron micrographs showed changes in the structure of intermediate filaments when MT4 cells were treated with an anti-HIV leukocyte extract. Changes in the structure of intermediate filaments were also observed in vimentin knockdown MT4 cells. A synthetic peptide derived from a cytoskeleton protein showed potent inhibitory activity on HIV-1 infection, and low cytotoxicity. Our data suggest that vimentin can be a suitable target to inhibit HIV-1.http://www.mdpi.com/1999-4915/8/6/98leukocyte extractvimentinintermediate filamentscytoskeletonHIVanti-HIV activityproteomics
spellingShingle Celia Fernández-Ortega
Anna Ramírez
Dionne Casillas
Taimi Paneque
Raimundo Ubieta
Marta Dubed
Leonor Navea
Lila Castellanos-Serra
Carlos Duarte
Viviana Falcon
Osvaldo Reyes
Hilda Garay
Eladio Silva
Enrique Noa
Yassel Ramos
Vladimir Besada
Lázaro Betancourt
Identification of Vimentin as a Potential Therapeutic Target against HIV Infection
Viruses
leukocyte extract
vimentin
intermediate filaments
cytoskeleton
HIV
anti-HIV activity
proteomics
title Identification of Vimentin as a Potential Therapeutic Target against HIV Infection
title_full Identification of Vimentin as a Potential Therapeutic Target against HIV Infection
title_fullStr Identification of Vimentin as a Potential Therapeutic Target against HIV Infection
title_full_unstemmed Identification of Vimentin as a Potential Therapeutic Target against HIV Infection
title_short Identification of Vimentin as a Potential Therapeutic Target against HIV Infection
title_sort identification of vimentin as a potential therapeutic target against hiv infection
topic leukocyte extract
vimentin
intermediate filaments
cytoskeleton
HIV
anti-HIV activity
proteomics
url http://www.mdpi.com/1999-4915/8/6/98
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