Combining 25-hydroxycholesterol with an HIV fusion inhibitor peptide: Interaction with biomembrane model systems and human blood cells
- Autores
- Gomes, Bárbara; Sanna, Giusepinna; Madeddu, Silvia; Hollmann, Axel; Santos, Nuno C.
- Año de publicación
- 2019
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- The fusion between the viral and the target cell membrane is a crucial step in the life cycle of enveloped viruses. The blocking of this process is a well-known therapeutic approach that led to the development of the fusion inhibitor peptide enfuvirtide, clinically used against human immunodeficiency virus (HIV) type 1. Despite this significant advance on viral treatment, the appearance of resistance has limited its clinical use. Such a limitation has led to the development of other fusion inhibitor peptides, such as C34, that present the same structural domain as enfuvirtide (heptad repeat sequence) but have different functional domains (pocket-binding domain in the case of C34 and lipid-binding domain in the case of enfuvirtide). Recently, the antiviral properties of 25-hydroxycholesterol were demonstrated, which boosted the interest in this oxysterol. The combination of two distinct antiviral molecules, C34 and 25-hydroxycholesterol, may help to suppress the emergence of resistant viruses. In this work, we characterized the interaction of the C34-25-hydroxycholesterol conjugate with biomembrane model systems and human blood cells. Lipid vesicles and monolayers with defined lipid compositions were used as biomembrane model systems. The conjugate interacts preferentially with membranes rich in sphingomyelin (a lipid enriched in lipid rafts) and presents a poor partition to membranes composed solely of phosphatidylcholine and cholesterol. We hypothesize that cholesterol causes a repulsive effect that is overcome in the presence of sphingomyelin. Importantly, the peptide shows a preference for human peripheral blood mononuclear cells relative to erythrocytes, which shows its potential to target CD4 + cells. Antiviral activity results against different wild-type and drug-resistant HIV strains further demonstrated the potential of C34-HC as a good candidate for future studies.
Fil: Gomes, Bárbara. Universidade Nova de Lisboa. Faculdade de Ciencias Medicas; Portugal
Fil: Sanna, Giusepinna. University of Cagliary; Italia
Fil: Madeddu, Silvia. University of Cagliary; Italia
Fil: Hollmann, Axel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Centro de Investigación en Biofísica Aplicada y Alimentos. - Universidad Nacional de Santiago del Estero. Centro de Investigación en Biofísica Aplicada y Alimentos; Argentina. Universidad Nacional de Quilmes; Argentina
Fil: Santos, Nuno C.. Universidade Nova de Lisboa. Faculdade de Ciencias Medicas; Portugal - Materia
-
25-HYDROXYCHOLESTEROL
C34
FUSION
HUMAN IMMUNODEFICIENCY VIRUS
PEPTIDE - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/147263
Ver los metadatos del registro completo
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CONICET Digital (CONICET) |
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Combining 25-hydroxycholesterol with an HIV fusion inhibitor peptide: Interaction with biomembrane model systems and human blood cellsGomes, BárbaraSanna, GiusepinnaMadeddu, SilviaHollmann, AxelSantos, Nuno C.25-HYDROXYCHOLESTEROLC34FUSIONHUMAN IMMUNODEFICIENCY VIRUSPEPTIDEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The fusion between the viral and the target cell membrane is a crucial step in the life cycle of enveloped viruses. The blocking of this process is a well-known therapeutic approach that led to the development of the fusion inhibitor peptide enfuvirtide, clinically used against human immunodeficiency virus (HIV) type 1. Despite this significant advance on viral treatment, the appearance of resistance has limited its clinical use. Such a limitation has led to the development of other fusion inhibitor peptides, such as C34, that present the same structural domain as enfuvirtide (heptad repeat sequence) but have different functional domains (pocket-binding domain in the case of C34 and lipid-binding domain in the case of enfuvirtide). Recently, the antiviral properties of 25-hydroxycholesterol were demonstrated, which boosted the interest in this oxysterol. The combination of two distinct antiviral molecules, C34 and 25-hydroxycholesterol, may help to suppress the emergence of resistant viruses. In this work, we characterized the interaction of the C34-25-hydroxycholesterol conjugate with biomembrane model systems and human blood cells. Lipid vesicles and monolayers with defined lipid compositions were used as biomembrane model systems. The conjugate interacts preferentially with membranes rich in sphingomyelin (a lipid enriched in lipid rafts) and presents a poor partition to membranes composed solely of phosphatidylcholine and cholesterol. We hypothesize that cholesterol causes a repulsive effect that is overcome in the presence of sphingomyelin. Importantly, the peptide shows a preference for human peripheral blood mononuclear cells relative to erythrocytes, which shows its potential to target CD4 + cells. Antiviral activity results against different wild-type and drug-resistant HIV strains further demonstrated the potential of C34-HC as a good candidate for future studies.Fil: Gomes, Bárbara. Universidade Nova de Lisboa. Faculdade de Ciencias Medicas; PortugalFil: Sanna, Giusepinna. University of Cagliary; ItaliaFil: Madeddu, Silvia. University of Cagliary; ItaliaFil: Hollmann, Axel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Centro de Investigación en Biofísica Aplicada y Alimentos. - Universidad Nacional de Santiago del Estero. Centro de Investigación en Biofísica Aplicada y Alimentos; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Santos, Nuno C.. Universidade Nova de Lisboa. Faculdade de Ciencias Medicas; PortugalAmerican Chemical Society2019-02-28info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/147263Gomes, Bárbara; Sanna, Giusepinna; Madeddu, Silvia; Hollmann, Axel; Santos, Nuno C.; Combining 25-hydroxycholesterol with an HIV fusion inhibitor peptide: Interaction with biomembrane model systems and human blood cells; American Chemical Society; Infectious Diseases; 5; 4; 28-2-2019; 582-5912373-8227CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/10.1021/acsinfecdis.8b00321info:eu-repo/semantics/altIdentifier/doi/10.1021/acsinfecdis.8b00321info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:57:22Zoai:ri.conicet.gov.ar:11336/147263instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:57:22.773CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Combining 25-hydroxycholesterol with an HIV fusion inhibitor peptide: Interaction with biomembrane model systems and human blood cells |
title |
Combining 25-hydroxycholesterol with an HIV fusion inhibitor peptide: Interaction with biomembrane model systems and human blood cells |
spellingShingle |
Combining 25-hydroxycholesterol with an HIV fusion inhibitor peptide: Interaction with biomembrane model systems and human blood cells Gomes, Bárbara 25-HYDROXYCHOLESTEROL C34 FUSION HUMAN IMMUNODEFICIENCY VIRUS PEPTIDE |
title_short |
Combining 25-hydroxycholesterol with an HIV fusion inhibitor peptide: Interaction with biomembrane model systems and human blood cells |
title_full |
Combining 25-hydroxycholesterol with an HIV fusion inhibitor peptide: Interaction with biomembrane model systems and human blood cells |
title_fullStr |
Combining 25-hydroxycholesterol with an HIV fusion inhibitor peptide: Interaction with biomembrane model systems and human blood cells |
title_full_unstemmed |
Combining 25-hydroxycholesterol with an HIV fusion inhibitor peptide: Interaction with biomembrane model systems and human blood cells |
title_sort |
Combining 25-hydroxycholesterol with an HIV fusion inhibitor peptide: Interaction with biomembrane model systems and human blood cells |
dc.creator.none.fl_str_mv |
Gomes, Bárbara Sanna, Giusepinna Madeddu, Silvia Hollmann, Axel Santos, Nuno C. |
author |
Gomes, Bárbara |
author_facet |
Gomes, Bárbara Sanna, Giusepinna Madeddu, Silvia Hollmann, Axel Santos, Nuno C. |
author_role |
author |
author2 |
Sanna, Giusepinna Madeddu, Silvia Hollmann, Axel Santos, Nuno C. |
author2_role |
author author author author |
dc.subject.none.fl_str_mv |
25-HYDROXYCHOLESTEROL C34 FUSION HUMAN IMMUNODEFICIENCY VIRUS PEPTIDE |
topic |
25-HYDROXYCHOLESTEROL C34 FUSION HUMAN IMMUNODEFICIENCY VIRUS PEPTIDE |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
The fusion between the viral and the target cell membrane is a crucial step in the life cycle of enveloped viruses. The blocking of this process is a well-known therapeutic approach that led to the development of the fusion inhibitor peptide enfuvirtide, clinically used against human immunodeficiency virus (HIV) type 1. Despite this significant advance on viral treatment, the appearance of resistance has limited its clinical use. Such a limitation has led to the development of other fusion inhibitor peptides, such as C34, that present the same structural domain as enfuvirtide (heptad repeat sequence) but have different functional domains (pocket-binding domain in the case of C34 and lipid-binding domain in the case of enfuvirtide). Recently, the antiviral properties of 25-hydroxycholesterol were demonstrated, which boosted the interest in this oxysterol. The combination of two distinct antiviral molecules, C34 and 25-hydroxycholesterol, may help to suppress the emergence of resistant viruses. In this work, we characterized the interaction of the C34-25-hydroxycholesterol conjugate with biomembrane model systems and human blood cells. Lipid vesicles and monolayers with defined lipid compositions were used as biomembrane model systems. The conjugate interacts preferentially with membranes rich in sphingomyelin (a lipid enriched in lipid rafts) and presents a poor partition to membranes composed solely of phosphatidylcholine and cholesterol. We hypothesize that cholesterol causes a repulsive effect that is overcome in the presence of sphingomyelin. Importantly, the peptide shows a preference for human peripheral blood mononuclear cells relative to erythrocytes, which shows its potential to target CD4 + cells. Antiviral activity results against different wild-type and drug-resistant HIV strains further demonstrated the potential of C34-HC as a good candidate for future studies. Fil: Gomes, Bárbara. Universidade Nova de Lisboa. Faculdade de Ciencias Medicas; Portugal Fil: Sanna, Giusepinna. University of Cagliary; Italia Fil: Madeddu, Silvia. University of Cagliary; Italia Fil: Hollmann, Axel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Centro de Investigación en Biofísica Aplicada y Alimentos. - Universidad Nacional de Santiago del Estero. Centro de Investigación en Biofísica Aplicada y Alimentos; Argentina. Universidad Nacional de Quilmes; Argentina Fil: Santos, Nuno C.. Universidade Nova de Lisboa. Faculdade de Ciencias Medicas; Portugal |
description |
The fusion between the viral and the target cell membrane is a crucial step in the life cycle of enveloped viruses. The blocking of this process is a well-known therapeutic approach that led to the development of the fusion inhibitor peptide enfuvirtide, clinically used against human immunodeficiency virus (HIV) type 1. Despite this significant advance on viral treatment, the appearance of resistance has limited its clinical use. Such a limitation has led to the development of other fusion inhibitor peptides, such as C34, that present the same structural domain as enfuvirtide (heptad repeat sequence) but have different functional domains (pocket-binding domain in the case of C34 and lipid-binding domain in the case of enfuvirtide). Recently, the antiviral properties of 25-hydroxycholesterol were demonstrated, which boosted the interest in this oxysterol. The combination of two distinct antiviral molecules, C34 and 25-hydroxycholesterol, may help to suppress the emergence of resistant viruses. In this work, we characterized the interaction of the C34-25-hydroxycholesterol conjugate with biomembrane model systems and human blood cells. Lipid vesicles and monolayers with defined lipid compositions were used as biomembrane model systems. The conjugate interacts preferentially with membranes rich in sphingomyelin (a lipid enriched in lipid rafts) and presents a poor partition to membranes composed solely of phosphatidylcholine and cholesterol. We hypothesize that cholesterol causes a repulsive effect that is overcome in the presence of sphingomyelin. Importantly, the peptide shows a preference for human peripheral blood mononuclear cells relative to erythrocytes, which shows its potential to target CD4 + cells. Antiviral activity results against different wild-type and drug-resistant HIV strains further demonstrated the potential of C34-HC as a good candidate for future studies. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-02-28 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/147263 Gomes, Bárbara; Sanna, Giusepinna; Madeddu, Silvia; Hollmann, Axel; Santos, Nuno C.; Combining 25-hydroxycholesterol with an HIV fusion inhibitor peptide: Interaction with biomembrane model systems and human blood cells; American Chemical Society; Infectious Diseases; 5; 4; 28-2-2019; 582-591 2373-8227 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/147263 |
identifier_str_mv |
Gomes, Bárbara; Sanna, Giusepinna; Madeddu, Silvia; Hollmann, Axel; Santos, Nuno C.; Combining 25-hydroxycholesterol with an HIV fusion inhibitor peptide: Interaction with biomembrane model systems and human blood cells; American Chemical Society; Infectious Diseases; 5; 4; 28-2-2019; 582-591 2373-8227 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/10.1021/acsinfecdis.8b00321 info:eu-repo/semantics/altIdentifier/doi/10.1021/acsinfecdis.8b00321 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
American Chemical Society |
publisher.none.fl_str_mv |
American Chemical Society |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1844613716860993536 |
score |
13.070432 |