Polymorphisms in p1-p6/p6* of HIV Type 1 Can Delay Protease Autoprocessing and Increase Drug Susceptibility

Autores
Whitehurst, N.; Chappey, C.; Petropoulos, C.; Parkin, N.; Gamarnik, Andrea Vanesa
Año de publicación
2003
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Maturation of infectious human immunodeficiency virus type 1 (HIV-1) particles requires proteolytic cleavage of structural polyproteins by viral protease. Inhibition of protease is a powerful tool for the treatment of HIV infection. Using a well-established phenotypic drug susceptibility assay, we found that sequences outside of the protease gene can modulate the susceptibility to protease inhibitors (PIs). Chimeric viruses carrying p1-p6/p6* sequences from patient isolates in the context of an NL4-3 molecular clone exhibited increased PI susceptibility. Furthermore, this phenotype was associated with a delay in protease autoprocessing in virions and a reduction in replication capacity. We propose that the interplay between protease and the C terminus of Gag is critical for proper protease activity and mismatches between these regions can reduce viral replication and increase drug susceptibility.
Fil: Whitehurst, N.. ViroLogic; Estados Unidos
Fil: Chappey, C.. ViroLogic; Estados Unidos
Fil: Petropoulos, C.. ViroLogic; Estados Unidos
Fil: Parkin, N.. ViroLogic; Estados Unidos
Fil: Gamarnik, Andrea Vanesa. ViroLogic; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Materia
Hiv
Drug Susceptibility
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/45199
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/45199
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Polymorphisms in p1-p6/p6* of HIV Type 1 Can Delay Protease Autoprocessing and Increase Drug SusceptibilityWhitehurst, N.Chappey, C.Petropoulos, C.Parkin, N.Gamarnik, Andrea VanesaHivDrug Susceptibilityhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Maturation of infectious human immunodeficiency virus type 1 (HIV-1) particles requires proteolytic cleavage of structural polyproteins by viral protease. Inhibition of protease is a powerful tool for the treatment of HIV infection. Using a well-established phenotypic drug susceptibility assay, we found that sequences outside of the protease gene can modulate the susceptibility to protease inhibitors (PIs). Chimeric viruses carrying p1-p6/p6* sequences from patient isolates in the context of an NL4-3 molecular clone exhibited increased PI susceptibility. Furthermore, this phenotype was associated with a delay in protease autoprocessing in virions and a reduction in replication capacity. We propose that the interplay between protease and the C terminus of Gag is critical for proper protease activity and mismatches between these regions can reduce viral replication and increase drug susceptibility.Fil: Whitehurst, N.. ViroLogic; Estados UnidosFil: Chappey, C.. ViroLogic; Estados UnidosFil: Petropoulos, C.. ViroLogic; Estados UnidosFil: Parkin, N.. ViroLogic; Estados UnidosFil: Gamarnik, Andrea Vanesa. ViroLogic; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaMary Ann Liebert2003-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/45199Whitehurst, N.; Chappey, C.; Petropoulos, C.; Parkin, N.; Gamarnik, Andrea Vanesa; Polymorphisms in p1-p6/p6* of HIV Type 1 Can Delay Protease Autoprocessing and Increase Drug Susceptibility; Mary Ann Liebert; Aids Research and Human Retroviruses; 19; 9; 9-2003; 779-7840889-22291931-8405CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.liebertpub.com/doi/abs/10.1089/088922203769232575info:eu-repo/semantics/altIdentifier/doi/10.1089/088922203769232575info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:14:48Zoai:ri.conicet.gov.ar:11336/45199instacron: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:34982025-10-22 12:14:48.414CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Polymorphisms in p1-p6/p6* of HIV Type 1 Can Delay Protease Autoprocessing and Increase Drug Susceptibility
title Polymorphisms in p1-p6/p6* of HIV Type 1 Can Delay Protease Autoprocessing and Increase Drug Susceptibility
spellingShingle Polymorphisms in p1-p6/p6* of HIV Type 1 Can Delay Protease Autoprocessing and Increase Drug Susceptibility
Whitehurst, N.
Hiv
Drug Susceptibility
title_short Polymorphisms in p1-p6/p6* of HIV Type 1 Can Delay Protease Autoprocessing and Increase Drug Susceptibility
title_full Polymorphisms in p1-p6/p6* of HIV Type 1 Can Delay Protease Autoprocessing and Increase Drug Susceptibility
title_fullStr Polymorphisms in p1-p6/p6* of HIV Type 1 Can Delay Protease Autoprocessing and Increase Drug Susceptibility
title_full_unstemmed Polymorphisms in p1-p6/p6* of HIV Type 1 Can Delay Protease Autoprocessing and Increase Drug Susceptibility
title_sort Polymorphisms in p1-p6/p6* of HIV Type 1 Can Delay Protease Autoprocessing and Increase Drug Susceptibility
dc.creator.none.fl_str_mv Whitehurst, N.
Chappey, C.
Petropoulos, C.
Parkin, N.
Gamarnik, Andrea Vanesa
author Whitehurst, N.
author_facet Whitehurst, N.
Chappey, C.
Petropoulos, C.
Parkin, N.
Gamarnik, Andrea Vanesa
author_role author
author2 Chappey, C.
Petropoulos, C.
Parkin, N.
Gamarnik, Andrea Vanesa
author2_role author
author
author
author
dc.subject.none.fl_str_mv Hiv
Drug Susceptibility
topic Hiv
Drug Susceptibility
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Maturation of infectious human immunodeficiency virus type 1 (HIV-1) particles requires proteolytic cleavage of structural polyproteins by viral protease. Inhibition of protease is a powerful tool for the treatment of HIV infection. Using a well-established phenotypic drug susceptibility assay, we found that sequences outside of the protease gene can modulate the susceptibility to protease inhibitors (PIs). Chimeric viruses carrying p1-p6/p6* sequences from patient isolates in the context of an NL4-3 molecular clone exhibited increased PI susceptibility. Furthermore, this phenotype was associated with a delay in protease autoprocessing in virions and a reduction in replication capacity. We propose that the interplay between protease and the C terminus of Gag is critical for proper protease activity and mismatches between these regions can reduce viral replication and increase drug susceptibility.
Fil: Whitehurst, N.. ViroLogic; Estados Unidos
Fil: Chappey, C.. ViroLogic; Estados Unidos
Fil: Petropoulos, C.. ViroLogic; Estados Unidos
Fil: Parkin, N.. ViroLogic; Estados Unidos
Fil: Gamarnik, Andrea Vanesa. ViroLogic; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
description Maturation of infectious human immunodeficiency virus type 1 (HIV-1) particles requires proteolytic cleavage of structural polyproteins by viral protease. Inhibition of protease is a powerful tool for the treatment of HIV infection. Using a well-established phenotypic drug susceptibility assay, we found that sequences outside of the protease gene can modulate the susceptibility to protease inhibitors (PIs). Chimeric viruses carrying p1-p6/p6* sequences from patient isolates in the context of an NL4-3 molecular clone exhibited increased PI susceptibility. Furthermore, this phenotype was associated with a delay in protease autoprocessing in virions and a reduction in replication capacity. We propose that the interplay between protease and the C terminus of Gag is critical for proper protease activity and mismatches between these regions can reduce viral replication and increase drug susceptibility.
publishDate 2003
dc.date.none.fl_str_mv 2003-09
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/11336/45199
Whitehurst, N.; Chappey, C.; Petropoulos, C.; Parkin, N.; Gamarnik, Andrea Vanesa; Polymorphisms in p1-p6/p6* of HIV Type 1 Can Delay Protease Autoprocessing and Increase Drug Susceptibility; Mary Ann Liebert; Aids Research and Human Retroviruses; 19; 9; 9-2003; 779-784
0889-2229
1931-8405
CONICET Digital
CONICET
url http://hdl.handle.net/11336/45199
identifier_str_mv Whitehurst, N.; Chappey, C.; Petropoulos, C.; Parkin, N.; Gamarnik, Andrea Vanesa; Polymorphisms in p1-p6/p6* of HIV Type 1 Can Delay Protease Autoprocessing and Increase Drug Susceptibility; Mary Ann Liebert; Aids Research and Human Retroviruses; 19; 9; 9-2003; 779-784
0889-2229
1931-8405
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.liebertpub.com/doi/abs/10.1089/088922203769232575
info:eu-repo/semantics/altIdentifier/doi/10.1089/088922203769232575
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
dc.publisher.none.fl_str_mv Mary Ann Liebert
publisher.none.fl_str_mv Mary Ann Liebert
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)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846782557840998400
score 12.982451

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