Antiviral activity of recombinant ankyrin targeted to the capsid domain of HIV-1 Gag polyprotein
Background Ankyrins are cellular mediators of a number of essential protein-protein interactions. Unlike intrabodies, ankyrins are composed of highly structured repeat modules characterized by disulfide bridge-independent folding. Artificial ankyrin molecules, designed to target viral components, mi...
Ausführliche Beschreibung
Autor*in: |
Nangola, Sawitree [verfasserIn] |
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E-Artikel |
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Englisch |
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2012 |
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Anmerkung: |
© Nangola et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( |
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Übergeordnetes Werk: |
Enthalten in: Retrovirology - London : BioMed Central, 2004, 9(2012), 1 vom: 20. Feb. |
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Übergeordnetes Werk: |
volume:9 ; year:2012 ; number:1 ; day:20 ; month:02 |
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DOI / URN: |
10.1186/1742-4690-9-17 |
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Katalog-ID: |
SPR029161215 |
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041 | |a eng | ||
100 | 1 | |a Nangola, Sawitree |e verfasserin |4 aut | |
245 | 1 | 0 | |a Antiviral activity of recombinant ankyrin targeted to the capsid domain of HIV-1 Gag polyprotein |
264 | 1 | |c 2012 | |
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337 | |a Computermedien |b c |2 rdamedia | ||
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500 | |a © Nangola et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( | ||
520 | |a Background Ankyrins are cellular mediators of a number of essential protein-protein interactions. Unlike intrabodies, ankyrins are composed of highly structured repeat modules characterized by disulfide bridge-independent folding. Artificial ankyrin molecules, designed to target viral components, might act as intracellular antiviral agents and contribute to the cellular immunity against viral pathogens such as HIV-1. Results A phage-displayed library of artificial ankyrins was constructed, and screened on a polyprotein made of the fused matrix and capsid domains (MA-CA) of the HIV-1 Gag precursor. An ankyrin with three modules named $ Ank^{GAG} $1D4 (16.5 kDa) was isolated. $ Ank^{GAG} $1D4 and MA-CA formed a protein complex with a stoichiometry of 1:1 and a dissociation constant of Kd ~ 1 μM, and the $ Ank^{GAG} $1D4 binding site was mapped to the N-terminal domain of the CA, within residues 1-110. HIV-1 production in SupT1 cells stably expressing $ Ank^{GAG} $1D4 in both N-myristoylated and non-N-myristoylated versions was significantly reduced compared to control cells. $ Ank^{GAG} $1D4 expression also reduced the production of MLV, a phylogenetically distant retrovirus. The $ Ank^{GAG} $1D4-mediated antiviral effect on HIV-1 was found to occur at post-integration steps, but did not involve the Gag precursor processing or cellular trafficking. Our data suggested that the lower HIV-1 progeny yields resulted from the negative interference of $ Ank^{GAG} $1D4-CA with the Gag assembly and budding pathway. Conclusions The resistance of $ Ank^{GAG} $1D4-expressing cells to HIV-1 suggested that the CA-targeted ankyrin $ Ank^{GAG} $1D4 could serve as a protein platform for the design of a novel class of intracellular inhibitors of HIV-1 assembly based on ankyrin-repeat modules. | ||
650 | 4 | |a HIV-1 |7 (dpeaa)DE-He213 | |
650 | 4 | |a HIV-1 assembly |7 (dpeaa)DE-He213 | |
650 | 4 | |a Gag polyprotein |7 (dpeaa)DE-He213 | |
650 | 4 | |a CA domain |7 (dpeaa)DE-He213 | |
650 | 4 | |a virus assembly inhibitor |7 (dpeaa)DE-He213 | |
650 | 4 | |a ankyrins |7 (dpeaa)DE-He213 | |
650 | 4 | |a artificial ankyrin library |7 (dpeaa)DE-He213 | |
650 | 4 | |a intracellular antiviral agent |7 (dpeaa)DE-He213 | |
700 | 1 | |a Urvoas, Agathe |4 aut | |
700 | 1 | |a Valerio-Lepiniec, Marie |4 aut | |
700 | 1 | |a Khamaikawin, Wannisa |4 aut | |
700 | 1 | |a Sakkhachornphop, Supachai |4 aut | |
700 | 1 | |a Hong, Saw-See |4 aut | |
700 | 1 | |a Boulanger, Pierre |4 aut | |
700 | 1 | |a Minard, Philippe |4 aut | |
700 | 1 | |a Tayapiwatana, Chatchai |4 aut | |
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912 | |a SSG-OLC-PHA | ||
912 | |a GBV_ILN_11 | ||
912 | |a GBV_ILN_20 | ||
912 | |a GBV_ILN_22 | ||
912 | |a GBV_ILN_23 | ||
912 | |a GBV_ILN_24 | ||
912 | |a GBV_ILN_31 | ||
912 | |a GBV_ILN_39 | ||
912 | |a GBV_ILN_40 | ||
912 | |a GBV_ILN_60 | ||
912 | |a GBV_ILN_62 | ||
912 | |a GBV_ILN_63 | ||
912 | |a GBV_ILN_65 | ||
912 | |a GBV_ILN_69 | ||
912 | |a GBV_ILN_70 | ||
912 | |a GBV_ILN_73 | ||
912 | |a GBV_ILN_74 | ||
912 | |a GBV_ILN_95 | ||
912 | |a GBV_ILN_105 | ||
912 | |a GBV_ILN_110 | ||
912 | |a GBV_ILN_151 | ||
912 | |a GBV_ILN_161 | ||
912 | |a GBV_ILN_170 | ||
912 | |a GBV_ILN_206 | ||
912 | |a GBV_ILN_213 | ||
912 | |a GBV_ILN_230 | ||
912 | |a GBV_ILN_285 | ||
912 | |a GBV_ILN_293 | ||
912 | |a GBV_ILN_602 | ||
912 | |a GBV_ILN_702 | ||
912 | |a GBV_ILN_2001 | ||
912 | |a GBV_ILN_2003 | ||
912 | |a GBV_ILN_2005 | ||
912 | |a GBV_ILN_2006 | ||
912 | |a GBV_ILN_2008 | ||
912 | |a GBV_ILN_2009 | ||
912 | |a GBV_ILN_2010 | ||
912 | |a GBV_ILN_2011 | ||
912 | |a GBV_ILN_2014 | ||
912 | |a GBV_ILN_2015 | ||
912 | |a GBV_ILN_2020 | ||
912 | |a GBV_ILN_2021 | ||
912 | |a GBV_ILN_2025 | ||
912 | |a GBV_ILN_2031 | ||
912 | |a GBV_ILN_2038 | ||
912 | |a GBV_ILN_2044 | ||
912 | |a GBV_ILN_2048 | ||
912 | |a GBV_ILN_2050 | ||
912 | |a GBV_ILN_2055 | ||
912 | |a GBV_ILN_2056 | ||
912 | |a GBV_ILN_2057 | ||
912 | |a GBV_ILN_2061 | ||
912 | |a GBV_ILN_2111 | ||
912 | |a GBV_ILN_2113 | ||
912 | |a GBV_ILN_2190 | ||
912 | |a GBV_ILN_4012 | ||
912 | |a GBV_ILN_4037 | ||
912 | |a GBV_ILN_4112 | ||
912 | |a GBV_ILN_4125 | ||
912 | |a GBV_ILN_4126 | ||
912 | |a GBV_ILN_4249 | ||
912 | |a GBV_ILN_4305 | ||
912 | |a GBV_ILN_4306 | ||
912 | |a GBV_ILN_4307 | ||
912 | |a GBV_ILN_4313 | ||
912 | |a GBV_ILN_4322 | ||
912 | |a GBV_ILN_4323 | ||
912 | |a GBV_ILN_4324 | ||
912 | |a GBV_ILN_4325 | ||
912 | |a GBV_ILN_4338 | ||
912 | |a GBV_ILN_4367 | ||
912 | |a GBV_ILN_4700 | ||
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10.1186/1742-4690-9-17 doi (DE-627)SPR029161215 (SPR)1742-4690-9-17-e DE-627 ger DE-627 rakwb eng Nangola, Sawitree verfasserin aut Antiviral activity of recombinant ankyrin targeted to the capsid domain of HIV-1 Gag polyprotein 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Nangola et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Ankyrins are cellular mediators of a number of essential protein-protein interactions. Unlike intrabodies, ankyrins are composed of highly structured repeat modules characterized by disulfide bridge-independent folding. Artificial ankyrin molecules, designed to target viral components, might act as intracellular antiviral agents and contribute to the cellular immunity against viral pathogens such as HIV-1. Results A phage-displayed library of artificial ankyrins was constructed, and screened on a polyprotein made of the fused matrix and capsid domains (MA-CA) of the HIV-1 Gag precursor. An ankyrin with three modules named $ Ank^{GAG} $1D4 (16.5 kDa) was isolated. $ Ank^{GAG} $1D4 and MA-CA formed a protein complex with a stoichiometry of 1:1 and a dissociation constant of Kd ~ 1 μM, and the $ Ank^{GAG} $1D4 binding site was mapped to the N-terminal domain of the CA, within residues 1-110. HIV-1 production in SupT1 cells stably expressing $ Ank^{GAG} $1D4 in both N-myristoylated and non-N-myristoylated versions was significantly reduced compared to control cells. $ Ank^{GAG} $1D4 expression also reduced the production of MLV, a phylogenetically distant retrovirus. The $ Ank^{GAG} $1D4-mediated antiviral effect on HIV-1 was found to occur at post-integration steps, but did not involve the Gag precursor processing or cellular trafficking. Our data suggested that the lower HIV-1 progeny yields resulted from the negative interference of $ Ank^{GAG} $1D4-CA with the Gag assembly and budding pathway. Conclusions The resistance of $ Ank^{GAG} $1D4-expressing cells to HIV-1 suggested that the CA-targeted ankyrin $ Ank^{GAG} $1D4 could serve as a protein platform for the design of a novel class of intracellular inhibitors of HIV-1 assembly based on ankyrin-repeat modules. HIV-1 (dpeaa)DE-He213 HIV-1 assembly (dpeaa)DE-He213 Gag polyprotein (dpeaa)DE-He213 CA domain (dpeaa)DE-He213 virus assembly inhibitor (dpeaa)DE-He213 ankyrins (dpeaa)DE-He213 artificial ankyrin library (dpeaa)DE-He213 intracellular antiviral agent (dpeaa)DE-He213 Urvoas, Agathe aut Valerio-Lepiniec, Marie aut Khamaikawin, Wannisa aut Sakkhachornphop, Supachai aut Hong, Saw-See aut Boulanger, Pierre aut Minard, Philippe aut Tayapiwatana, Chatchai aut Enthalten in Retrovirology London : BioMed Central, 2004 9(2012), 1 vom: 20. Feb. (DE-627)385612931 (DE-600)2142602-8 1742-4690 nnns volume:9 year:2012 number:1 day:20 month:02 https://dx.doi.org/10.1186/1742-4690-9-17 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2012 1 20 02 |
spelling |
10.1186/1742-4690-9-17 doi (DE-627)SPR029161215 (SPR)1742-4690-9-17-e DE-627 ger DE-627 rakwb eng Nangola, Sawitree verfasserin aut Antiviral activity of recombinant ankyrin targeted to the capsid domain of HIV-1 Gag polyprotein 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Nangola et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Ankyrins are cellular mediators of a number of essential protein-protein interactions. Unlike intrabodies, ankyrins are composed of highly structured repeat modules characterized by disulfide bridge-independent folding. Artificial ankyrin molecules, designed to target viral components, might act as intracellular antiviral agents and contribute to the cellular immunity against viral pathogens such as HIV-1. Results A phage-displayed library of artificial ankyrins was constructed, and screened on a polyprotein made of the fused matrix and capsid domains (MA-CA) of the HIV-1 Gag precursor. An ankyrin with three modules named $ Ank^{GAG} $1D4 (16.5 kDa) was isolated. $ Ank^{GAG} $1D4 and MA-CA formed a protein complex with a stoichiometry of 1:1 and a dissociation constant of Kd ~ 1 μM, and the $ Ank^{GAG} $1D4 binding site was mapped to the N-terminal domain of the CA, within residues 1-110. HIV-1 production in SupT1 cells stably expressing $ Ank^{GAG} $1D4 in both N-myristoylated and non-N-myristoylated versions was significantly reduced compared to control cells. $ Ank^{GAG} $1D4 expression also reduced the production of MLV, a phylogenetically distant retrovirus. The $ Ank^{GAG} $1D4-mediated antiviral effect on HIV-1 was found to occur at post-integration steps, but did not involve the Gag precursor processing or cellular trafficking. Our data suggested that the lower HIV-1 progeny yields resulted from the negative interference of $ Ank^{GAG} $1D4-CA with the Gag assembly and budding pathway. Conclusions The resistance of $ Ank^{GAG} $1D4-expressing cells to HIV-1 suggested that the CA-targeted ankyrin $ Ank^{GAG} $1D4 could serve as a protein platform for the design of a novel class of intracellular inhibitors of HIV-1 assembly based on ankyrin-repeat modules. HIV-1 (dpeaa)DE-He213 HIV-1 assembly (dpeaa)DE-He213 Gag polyprotein (dpeaa)DE-He213 CA domain (dpeaa)DE-He213 virus assembly inhibitor (dpeaa)DE-He213 ankyrins (dpeaa)DE-He213 artificial ankyrin library (dpeaa)DE-He213 intracellular antiviral agent (dpeaa)DE-He213 Urvoas, Agathe aut Valerio-Lepiniec, Marie aut Khamaikawin, Wannisa aut Sakkhachornphop, Supachai aut Hong, Saw-See aut Boulanger, Pierre aut Minard, Philippe aut Tayapiwatana, Chatchai aut Enthalten in Retrovirology London : BioMed Central, 2004 9(2012), 1 vom: 20. Feb. (DE-627)385612931 (DE-600)2142602-8 1742-4690 nnns volume:9 year:2012 number:1 day:20 month:02 https://dx.doi.org/10.1186/1742-4690-9-17 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2012 1 20 02 |
allfields_unstemmed |
10.1186/1742-4690-9-17 doi (DE-627)SPR029161215 (SPR)1742-4690-9-17-e DE-627 ger DE-627 rakwb eng Nangola, Sawitree verfasserin aut Antiviral activity of recombinant ankyrin targeted to the capsid domain of HIV-1 Gag polyprotein 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Nangola et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Ankyrins are cellular mediators of a number of essential protein-protein interactions. Unlike intrabodies, ankyrins are composed of highly structured repeat modules characterized by disulfide bridge-independent folding. Artificial ankyrin molecules, designed to target viral components, might act as intracellular antiviral agents and contribute to the cellular immunity against viral pathogens such as HIV-1. Results A phage-displayed library of artificial ankyrins was constructed, and screened on a polyprotein made of the fused matrix and capsid domains (MA-CA) of the HIV-1 Gag precursor. An ankyrin with three modules named $ Ank^{GAG} $1D4 (16.5 kDa) was isolated. $ Ank^{GAG} $1D4 and MA-CA formed a protein complex with a stoichiometry of 1:1 and a dissociation constant of Kd ~ 1 μM, and the $ Ank^{GAG} $1D4 binding site was mapped to the N-terminal domain of the CA, within residues 1-110. HIV-1 production in SupT1 cells stably expressing $ Ank^{GAG} $1D4 in both N-myristoylated and non-N-myristoylated versions was significantly reduced compared to control cells. $ Ank^{GAG} $1D4 expression also reduced the production of MLV, a phylogenetically distant retrovirus. The $ Ank^{GAG} $1D4-mediated antiviral effect on HIV-1 was found to occur at post-integration steps, but did not involve the Gag precursor processing or cellular trafficking. Our data suggested that the lower HIV-1 progeny yields resulted from the negative interference of $ Ank^{GAG} $1D4-CA with the Gag assembly and budding pathway. Conclusions The resistance of $ Ank^{GAG} $1D4-expressing cells to HIV-1 suggested that the CA-targeted ankyrin $ Ank^{GAG} $1D4 could serve as a protein platform for the design of a novel class of intracellular inhibitors of HIV-1 assembly based on ankyrin-repeat modules. HIV-1 (dpeaa)DE-He213 HIV-1 assembly (dpeaa)DE-He213 Gag polyprotein (dpeaa)DE-He213 CA domain (dpeaa)DE-He213 virus assembly inhibitor (dpeaa)DE-He213 ankyrins (dpeaa)DE-He213 artificial ankyrin library (dpeaa)DE-He213 intracellular antiviral agent (dpeaa)DE-He213 Urvoas, Agathe aut Valerio-Lepiniec, Marie aut Khamaikawin, Wannisa aut Sakkhachornphop, Supachai aut Hong, Saw-See aut Boulanger, Pierre aut Minard, Philippe aut Tayapiwatana, Chatchai aut Enthalten in Retrovirology London : BioMed Central, 2004 9(2012), 1 vom: 20. Feb. (DE-627)385612931 (DE-600)2142602-8 1742-4690 nnns volume:9 year:2012 number:1 day:20 month:02 https://dx.doi.org/10.1186/1742-4690-9-17 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2012 1 20 02 |
allfieldsGer |
10.1186/1742-4690-9-17 doi (DE-627)SPR029161215 (SPR)1742-4690-9-17-e DE-627 ger DE-627 rakwb eng Nangola, Sawitree verfasserin aut Antiviral activity of recombinant ankyrin targeted to the capsid domain of HIV-1 Gag polyprotein 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Nangola et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Ankyrins are cellular mediators of a number of essential protein-protein interactions. Unlike intrabodies, ankyrins are composed of highly structured repeat modules characterized by disulfide bridge-independent folding. Artificial ankyrin molecules, designed to target viral components, might act as intracellular antiviral agents and contribute to the cellular immunity against viral pathogens such as HIV-1. Results A phage-displayed library of artificial ankyrins was constructed, and screened on a polyprotein made of the fused matrix and capsid domains (MA-CA) of the HIV-1 Gag precursor. An ankyrin with three modules named $ Ank^{GAG} $1D4 (16.5 kDa) was isolated. $ Ank^{GAG} $1D4 and MA-CA formed a protein complex with a stoichiometry of 1:1 and a dissociation constant of Kd ~ 1 μM, and the $ Ank^{GAG} $1D4 binding site was mapped to the N-terminal domain of the CA, within residues 1-110. HIV-1 production in SupT1 cells stably expressing $ Ank^{GAG} $1D4 in both N-myristoylated and non-N-myristoylated versions was significantly reduced compared to control cells. $ Ank^{GAG} $1D4 expression also reduced the production of MLV, a phylogenetically distant retrovirus. The $ Ank^{GAG} $1D4-mediated antiviral effect on HIV-1 was found to occur at post-integration steps, but did not involve the Gag precursor processing or cellular trafficking. Our data suggested that the lower HIV-1 progeny yields resulted from the negative interference of $ Ank^{GAG} $1D4-CA with the Gag assembly and budding pathway. Conclusions The resistance of $ Ank^{GAG} $1D4-expressing cells to HIV-1 suggested that the CA-targeted ankyrin $ Ank^{GAG} $1D4 could serve as a protein platform for the design of a novel class of intracellular inhibitors of HIV-1 assembly based on ankyrin-repeat modules. HIV-1 (dpeaa)DE-He213 HIV-1 assembly (dpeaa)DE-He213 Gag polyprotein (dpeaa)DE-He213 CA domain (dpeaa)DE-He213 virus assembly inhibitor (dpeaa)DE-He213 ankyrins (dpeaa)DE-He213 artificial ankyrin library (dpeaa)DE-He213 intracellular antiviral agent (dpeaa)DE-He213 Urvoas, Agathe aut Valerio-Lepiniec, Marie aut Khamaikawin, Wannisa aut Sakkhachornphop, Supachai aut Hong, Saw-See aut Boulanger, Pierre aut Minard, Philippe aut Tayapiwatana, Chatchai aut Enthalten in Retrovirology London : BioMed Central, 2004 9(2012), 1 vom: 20. Feb. (DE-627)385612931 (DE-600)2142602-8 1742-4690 nnns volume:9 year:2012 number:1 day:20 month:02 https://dx.doi.org/10.1186/1742-4690-9-17 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2012 1 20 02 |
allfieldsSound |
10.1186/1742-4690-9-17 doi (DE-627)SPR029161215 (SPR)1742-4690-9-17-e DE-627 ger DE-627 rakwb eng Nangola, Sawitree verfasserin aut Antiviral activity of recombinant ankyrin targeted to the capsid domain of HIV-1 Gag polyprotein 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Nangola et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Ankyrins are cellular mediators of a number of essential protein-protein interactions. Unlike intrabodies, ankyrins are composed of highly structured repeat modules characterized by disulfide bridge-independent folding. Artificial ankyrin molecules, designed to target viral components, might act as intracellular antiviral agents and contribute to the cellular immunity against viral pathogens such as HIV-1. Results A phage-displayed library of artificial ankyrins was constructed, and screened on a polyprotein made of the fused matrix and capsid domains (MA-CA) of the HIV-1 Gag precursor. An ankyrin with three modules named $ Ank^{GAG} $1D4 (16.5 kDa) was isolated. $ Ank^{GAG} $1D4 and MA-CA formed a protein complex with a stoichiometry of 1:1 and a dissociation constant of Kd ~ 1 μM, and the $ Ank^{GAG} $1D4 binding site was mapped to the N-terminal domain of the CA, within residues 1-110. HIV-1 production in SupT1 cells stably expressing $ Ank^{GAG} $1D4 in both N-myristoylated and non-N-myristoylated versions was significantly reduced compared to control cells. $ Ank^{GAG} $1D4 expression also reduced the production of MLV, a phylogenetically distant retrovirus. The $ Ank^{GAG} $1D4-mediated antiviral effect on HIV-1 was found to occur at post-integration steps, but did not involve the Gag precursor processing or cellular trafficking. Our data suggested that the lower HIV-1 progeny yields resulted from the negative interference of $ Ank^{GAG} $1D4-CA with the Gag assembly and budding pathway. Conclusions The resistance of $ Ank^{GAG} $1D4-expressing cells to HIV-1 suggested that the CA-targeted ankyrin $ Ank^{GAG} $1D4 could serve as a protein platform for the design of a novel class of intracellular inhibitors of HIV-1 assembly based on ankyrin-repeat modules. HIV-1 (dpeaa)DE-He213 HIV-1 assembly (dpeaa)DE-He213 Gag polyprotein (dpeaa)DE-He213 CA domain (dpeaa)DE-He213 virus assembly inhibitor (dpeaa)DE-He213 ankyrins (dpeaa)DE-He213 artificial ankyrin library (dpeaa)DE-He213 intracellular antiviral agent (dpeaa)DE-He213 Urvoas, Agathe aut Valerio-Lepiniec, Marie aut Khamaikawin, Wannisa aut Sakkhachornphop, Supachai aut Hong, Saw-See aut Boulanger, Pierre aut Minard, Philippe aut Tayapiwatana, Chatchai aut Enthalten in Retrovirology London : BioMed Central, 2004 9(2012), 1 vom: 20. Feb. (DE-627)385612931 (DE-600)2142602-8 1742-4690 nnns volume:9 year:2012 number:1 day:20 month:02 https://dx.doi.org/10.1186/1742-4690-9-17 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2012 1 20 02 |
language |
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Enthalten in Retrovirology 9(2012), 1 vom: 20. Feb. volume:9 year:2012 number:1 day:20 month:02 |
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HIV-1 HIV-1 assembly Gag polyprotein CA domain virus assembly inhibitor ankyrins artificial ankyrin library intracellular antiviral agent |
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Nangola, Sawitree @@aut@@ Urvoas, Agathe @@aut@@ Valerio-Lepiniec, Marie @@aut@@ Khamaikawin, Wannisa @@aut@@ Sakkhachornphop, Supachai @@aut@@ Hong, Saw-See @@aut@@ Boulanger, Pierre @@aut@@ Minard, Philippe @@aut@@ Tayapiwatana, Chatchai @@aut@@ |
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Nangola, Sawitree |
spellingShingle |
Nangola, Sawitree misc HIV-1 misc HIV-1 assembly misc Gag polyprotein misc CA domain misc virus assembly inhibitor misc ankyrins misc artificial ankyrin library misc intracellular antiviral agent Antiviral activity of recombinant ankyrin targeted to the capsid domain of HIV-1 Gag polyprotein |
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Antiviral activity of recombinant ankyrin targeted to the capsid domain of HIV-1 Gag polyprotein HIV-1 (dpeaa)DE-He213 HIV-1 assembly (dpeaa)DE-He213 Gag polyprotein (dpeaa)DE-He213 CA domain (dpeaa)DE-He213 virus assembly inhibitor (dpeaa)DE-He213 ankyrins (dpeaa)DE-He213 artificial ankyrin library (dpeaa)DE-He213 intracellular antiviral agent (dpeaa)DE-He213 |
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misc HIV-1 misc HIV-1 assembly misc Gag polyprotein misc CA domain misc virus assembly inhibitor misc ankyrins misc artificial ankyrin library misc intracellular antiviral agent |
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Antiviral activity of recombinant ankyrin targeted to the capsid domain of HIV-1 Gag polyprotein |
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Antiviral activity of recombinant ankyrin targeted to the capsid domain of HIV-1 Gag polyprotein |
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Nangola, Sawitree Urvoas, Agathe Valerio-Lepiniec, Marie Khamaikawin, Wannisa Sakkhachornphop, Supachai Hong, Saw-See Boulanger, Pierre Minard, Philippe Tayapiwatana, Chatchai |
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title_sort |
antiviral activity of recombinant ankyrin targeted to the capsid domain of hiv-1 gag polyprotein |
title_auth |
Antiviral activity of recombinant ankyrin targeted to the capsid domain of HIV-1 Gag polyprotein |
abstract |
Background Ankyrins are cellular mediators of a number of essential protein-protein interactions. Unlike intrabodies, ankyrins are composed of highly structured repeat modules characterized by disulfide bridge-independent folding. Artificial ankyrin molecules, designed to target viral components, might act as intracellular antiviral agents and contribute to the cellular immunity against viral pathogens such as HIV-1. Results A phage-displayed library of artificial ankyrins was constructed, and screened on a polyprotein made of the fused matrix and capsid domains (MA-CA) of the HIV-1 Gag precursor. An ankyrin with three modules named $ Ank^{GAG} $1D4 (16.5 kDa) was isolated. $ Ank^{GAG} $1D4 and MA-CA formed a protein complex with a stoichiometry of 1:1 and a dissociation constant of Kd ~ 1 μM, and the $ Ank^{GAG} $1D4 binding site was mapped to the N-terminal domain of the CA, within residues 1-110. HIV-1 production in SupT1 cells stably expressing $ Ank^{GAG} $1D4 in both N-myristoylated and non-N-myristoylated versions was significantly reduced compared to control cells. $ Ank^{GAG} $1D4 expression also reduced the production of MLV, a phylogenetically distant retrovirus. The $ Ank^{GAG} $1D4-mediated antiviral effect on HIV-1 was found to occur at post-integration steps, but did not involve the Gag precursor processing or cellular trafficking. Our data suggested that the lower HIV-1 progeny yields resulted from the negative interference of $ Ank^{GAG} $1D4-CA with the Gag assembly and budding pathway. Conclusions The resistance of $ Ank^{GAG} $1D4-expressing cells to HIV-1 suggested that the CA-targeted ankyrin $ Ank^{GAG} $1D4 could serve as a protein platform for the design of a novel class of intracellular inhibitors of HIV-1 assembly based on ankyrin-repeat modules. © Nangola et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( |
abstractGer |
Background Ankyrins are cellular mediators of a number of essential protein-protein interactions. Unlike intrabodies, ankyrins are composed of highly structured repeat modules characterized by disulfide bridge-independent folding. Artificial ankyrin molecules, designed to target viral components, might act as intracellular antiviral agents and contribute to the cellular immunity against viral pathogens such as HIV-1. Results A phage-displayed library of artificial ankyrins was constructed, and screened on a polyprotein made of the fused matrix and capsid domains (MA-CA) of the HIV-1 Gag precursor. An ankyrin with three modules named $ Ank^{GAG} $1D4 (16.5 kDa) was isolated. $ Ank^{GAG} $1D4 and MA-CA formed a protein complex with a stoichiometry of 1:1 and a dissociation constant of Kd ~ 1 μM, and the $ Ank^{GAG} $1D4 binding site was mapped to the N-terminal domain of the CA, within residues 1-110. HIV-1 production in SupT1 cells stably expressing $ Ank^{GAG} $1D4 in both N-myristoylated and non-N-myristoylated versions was significantly reduced compared to control cells. $ Ank^{GAG} $1D4 expression also reduced the production of MLV, a phylogenetically distant retrovirus. The $ Ank^{GAG} $1D4-mediated antiviral effect on HIV-1 was found to occur at post-integration steps, but did not involve the Gag precursor processing or cellular trafficking. Our data suggested that the lower HIV-1 progeny yields resulted from the negative interference of $ Ank^{GAG} $1D4-CA with the Gag assembly and budding pathway. Conclusions The resistance of $ Ank^{GAG} $1D4-expressing cells to HIV-1 suggested that the CA-targeted ankyrin $ Ank^{GAG} $1D4 could serve as a protein platform for the design of a novel class of intracellular inhibitors of HIV-1 assembly based on ankyrin-repeat modules. © Nangola et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( |
abstract_unstemmed |
Background Ankyrins are cellular mediators of a number of essential protein-protein interactions. Unlike intrabodies, ankyrins are composed of highly structured repeat modules characterized by disulfide bridge-independent folding. Artificial ankyrin molecules, designed to target viral components, might act as intracellular antiviral agents and contribute to the cellular immunity against viral pathogens such as HIV-1. Results A phage-displayed library of artificial ankyrins was constructed, and screened on a polyprotein made of the fused matrix and capsid domains (MA-CA) of the HIV-1 Gag precursor. An ankyrin with three modules named $ Ank^{GAG} $1D4 (16.5 kDa) was isolated. $ Ank^{GAG} $1D4 and MA-CA formed a protein complex with a stoichiometry of 1:1 and a dissociation constant of Kd ~ 1 μM, and the $ Ank^{GAG} $1D4 binding site was mapped to the N-terminal domain of the CA, within residues 1-110. HIV-1 production in SupT1 cells stably expressing $ Ank^{GAG} $1D4 in both N-myristoylated and non-N-myristoylated versions was significantly reduced compared to control cells. $ Ank^{GAG} $1D4 expression also reduced the production of MLV, a phylogenetically distant retrovirus. The $ Ank^{GAG} $1D4-mediated antiviral effect on HIV-1 was found to occur at post-integration steps, but did not involve the Gag precursor processing or cellular trafficking. Our data suggested that the lower HIV-1 progeny yields resulted from the negative interference of $ Ank^{GAG} $1D4-CA with the Gag assembly and budding pathway. Conclusions The resistance of $ Ank^{GAG} $1D4-expressing cells to HIV-1 suggested that the CA-targeted ankyrin $ Ank^{GAG} $1D4 could serve as a protein platform for the design of a novel class of intracellular inhibitors of HIV-1 assembly based on ankyrin-repeat modules. © Nangola et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( |
collection_details |
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Antiviral activity of recombinant ankyrin targeted to the capsid domain of HIV-1 Gag polyprotein |
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https://dx.doi.org/10.1186/1742-4690-9-17 |
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Urvoas, Agathe Valerio-Lepiniec, Marie Khamaikawin, Wannisa Sakkhachornphop, Supachai Hong, Saw-See Boulanger, Pierre Minard, Philippe Tayapiwatana, Chatchai |
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Urvoas, Agathe Valerio-Lepiniec, Marie Khamaikawin, Wannisa Sakkhachornphop, Supachai Hong, Saw-See Boulanger, Pierre Minard, Philippe Tayapiwatana, Chatchai |
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An ankyrin with three modules named $ Ank^{GAG} $1D4 (16.5 kDa) was isolated. $ Ank^{GAG} $1D4 and MA-CA formed a protein complex with a stoichiometry of 1:1 and a dissociation constant of Kd ~ 1 μM, and the $ Ank^{GAG} $1D4 binding site was mapped to the N-terminal domain of the CA, within residues 1-110. HIV-1 production in SupT1 cells stably expressing $ Ank^{GAG} $1D4 in both N-myristoylated and non-N-myristoylated versions was significantly reduced compared to control cells. $ Ank^{GAG} $1D4 expression also reduced the production of MLV, a phylogenetically distant retrovirus. The $ Ank^{GAG} $1D4-mediated antiviral effect on HIV-1 was found to occur at post-integration steps, but did not involve the Gag precursor processing or cellular trafficking. Our data suggested that the lower HIV-1 progeny yields resulted from the negative interference of $ Ank^{GAG} $1D4-CA with the Gag assembly and budding pathway. Conclusions The resistance of $ Ank^{GAG} $1D4-expressing cells to HIV-1 suggested that the CA-targeted ankyrin $ Ank^{GAG} $1D4 could serve as a protein platform for the design of a novel class of intracellular inhibitors of HIV-1 assembly based on ankyrin-repeat modules.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">HIV-1</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">HIV-1 assembly</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Gag polyprotein</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">CA domain</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">virus assembly inhibitor</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">ankyrins</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">artificial ankyrin library</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">intracellular antiviral agent</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Urvoas, Agathe</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Valerio-Lepiniec, Marie</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Khamaikawin, Wannisa</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Sakkhachornphop, Supachai</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Hong, Saw-See</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Boulanger, Pierre</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Minard, Philippe</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Tayapiwatana, Chatchai</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Retrovirology</subfield><subfield code="d">London : BioMed Central, 2004</subfield><subfield code="g">9(2012), 1 vom: 20. 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score |
7.400346 |