HIV-1 subtype B and C integrase enzymes exhibit differential patterns of resistance to integrase inhibitors in biochemical assays
Because of high intersubtype HIV-1 genetic variability, it has been shown that subtype-specific patterns of resistance to antiretroviral drugs exist. We wished to ascertain whether this might be true for integrase inhibitors. We compared the susceptibility of subtype B and C HIV-1 integrase enzymes,...
Gespeichert in:
| Veröffentlicht in: | AIDS (London) 2010-09, Vol.24 (14), p.2171-2179 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2179 |
|---|---|
| container_issue | 14 |
| container_start_page | 2171 |
| container_title | AIDS (London) |
| container_volume | 24 |
| creator | BAR-MAGEN, Tamara DONAHUE, Daniel A MCDONOUGH, Emily I KUHL, Björn D FALTENBACHER, Verena H HONGTAO XU MICHAUD, Veronique SLOAN, Richard D WAINBERG, Mark A |
| description | Because of high intersubtype HIV-1 genetic variability, it has been shown that subtype-specific patterns of resistance to antiretroviral drugs exist. We wished to ascertain whether this might be true for integrase inhibitors.
We compared the susceptibility of subtype B and C HIV-1 integrase enzymes, harboring the previously reported resistance mutations E92Q, N155H, and E92Q/N155H, to clinically relevant integrase inhibitors. This was performed biochemically using a microtiter plate system.
Subtype C integrase enzymes bearing the resistance mutations E92Q/N155H were approximately 10-fold more susceptible to each of two integrase inhibitors, raltegravir and elvitegravir, than were subtype B recombinant integrase containing the same mutations.
Polymorphic differences within the subtype B and C integrase genes likely cause variations in the contribution of N155H alone or in combination with E92Q to drug resistance. It is possible that different viral subtypes may favor different mutational pathways, potentially leading to varying levels of drug resistance among different subtypes. |
| doi_str_mv | 10.1097/QAD.0b013e32833cf265 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_807288879</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>807288879</sourcerecordid><originalsourceid>FETCH-LOGICAL-c414t-29ac244f664723c9343d060f23a9dd25019d1de8491af6589a5c7fd4d9b07e293</originalsourceid><addsrcrecordid>eNqFkUtvFDEQhC0EIkvgHyDkC-I0of2YsX0MGyCRIiEk4Dry2G1itDuzuL0Sy41_jiHLQ1w4dR--qm5VMfZYwJkAZ56_Pb84gwmEQiWtUiHJob_DVkIb1fW9EXfZCuTgOqcMnLAHRJ8AoAdr77MTCYM2DuyKfbu8-tAJTvupHnbIX3A_R77mea74sXhCjvPXwxaJ45ebPOXKY04JC841-w3f-VqxzMSXxAtSpurngLwufxnk-adwKdRWPuUl3OA2h6b2RP5AD9m95DeEj47zlL1_9fLd-rK7fvP6an1-3QUtdO2k80FqnYb2uVTBKa0iDJCk8i5G2YNwUUS02gmfht463weToo5uAoPSqVP27NZ3V5bPe6Q6bjMF3Gz8jMueRgtGWmvN_0mjrbOmWTZS35KhLEQF07greevLYRQw_mhpbC2N_7bUZE-OB_bTFuNv0a9aGvD0CHhqSaXSYs30h1NSSzMY9R0j-5yZ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>748987293</pqid></control><display><type>article</type><title>HIV-1 subtype B and C integrase enzymes exhibit differential patterns of resistance to integrase inhibitors in biochemical assays</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Journals@Ovid Complete</source><creator>BAR-MAGEN, Tamara ; DONAHUE, Daniel A ; MCDONOUGH, Emily I ; KUHL, Björn D ; FALTENBACHER, Verena H ; HONGTAO XU ; MICHAUD, Veronique ; SLOAN, Richard D ; WAINBERG, Mark A</creator><creatorcontrib>BAR-MAGEN, Tamara ; DONAHUE, Daniel A ; MCDONOUGH, Emily I ; KUHL, Björn D ; FALTENBACHER, Verena H ; HONGTAO XU ; MICHAUD, Veronique ; SLOAN, Richard D ; WAINBERG, Mark A</creatorcontrib><description>Because of high intersubtype HIV-1 genetic variability, it has been shown that subtype-specific patterns of resistance to antiretroviral drugs exist. We wished to ascertain whether this might be true for integrase inhibitors.
We compared the susceptibility of subtype B and C HIV-1 integrase enzymes, harboring the previously reported resistance mutations E92Q, N155H, and E92Q/N155H, to clinically relevant integrase inhibitors. This was performed biochemically using a microtiter plate system.
Subtype C integrase enzymes bearing the resistance mutations E92Q/N155H were approximately 10-fold more susceptible to each of two integrase inhibitors, raltegravir and elvitegravir, than were subtype B recombinant integrase containing the same mutations.
Polymorphic differences within the subtype B and C integrase genes likely cause variations in the contribution of N155H alone or in combination with E92Q to drug resistance. It is possible that different viral subtypes may favor different mutational pathways, potentially leading to varying levels of drug resistance among different subtypes.</description><identifier>ISSN: 0269-9370</identifier><identifier>EISSN: 1473-5571</identifier><identifier>DOI: 10.1097/QAD.0b013e32833cf265</identifier><identifier>PMID: 20647908</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>AIDS/HIV ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiviral agents ; Biological and medical sciences ; Cells, Cultured ; DNA, Viral - drug effects ; DNA, Viral - genetics ; Drug Resistance, Viral - drug effects ; Drug Resistance, Viral - genetics ; Genetic Variation ; HIV Infections - drug therapy ; HIV Infections - genetics ; HIV Integrase - genetics ; HIV Integrase Inhibitors - pharmacology ; HIV-1 - drug effects ; HIV-1 - genetics ; Human immunodeficiency virus 1 ; Human viral diseases ; Humans ; Immunodeficiencies ; Immunodeficiencies. Immunoglobulinopathies ; Immunopathology ; Infectious diseases ; Medical sciences ; Mutation ; Pharmacology. Drug treatments ; Pyrrolidinones - pharmacology ; Raltegravir Potassium ; Sequence Analysis, DNA ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. Aids</subject><ispartof>AIDS (London), 2010-09, Vol.24 (14), p.2171-2179</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c414t-29ac244f664723c9343d060f23a9dd25019d1de8491af6589a5c7fd4d9b07e293</citedby><cites>FETCH-LOGICAL-c414t-29ac244f664723c9343d060f23a9dd25019d1de8491af6589a5c7fd4d9b07e293</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23242767$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20647908$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>BAR-MAGEN, Tamara</creatorcontrib><creatorcontrib>DONAHUE, Daniel A</creatorcontrib><creatorcontrib>MCDONOUGH, Emily I</creatorcontrib><creatorcontrib>KUHL, Björn D</creatorcontrib><creatorcontrib>FALTENBACHER, Verena H</creatorcontrib><creatorcontrib>HONGTAO XU</creatorcontrib><creatorcontrib>MICHAUD, Veronique</creatorcontrib><creatorcontrib>SLOAN, Richard D</creatorcontrib><creatorcontrib>WAINBERG, Mark A</creatorcontrib><title>HIV-1 subtype B and C integrase enzymes exhibit differential patterns of resistance to integrase inhibitors in biochemical assays</title><title>AIDS (London)</title><addtitle>AIDS</addtitle><description>Because of high intersubtype HIV-1 genetic variability, it has been shown that subtype-specific patterns of resistance to antiretroviral drugs exist. We wished to ascertain whether this might be true for integrase inhibitors.
We compared the susceptibility of subtype B and C HIV-1 integrase enzymes, harboring the previously reported resistance mutations E92Q, N155H, and E92Q/N155H, to clinically relevant integrase inhibitors. This was performed biochemically using a microtiter plate system.
Subtype C integrase enzymes bearing the resistance mutations E92Q/N155H were approximately 10-fold more susceptible to each of two integrase inhibitors, raltegravir and elvitegravir, than were subtype B recombinant integrase containing the same mutations.
Polymorphic differences within the subtype B and C integrase genes likely cause variations in the contribution of N155H alone or in combination with E92Q to drug resistance. It is possible that different viral subtypes may favor different mutational pathways, potentially leading to varying levels of drug resistance among different subtypes.</description><subject>AIDS/HIV</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiviral agents</subject><subject>Biological and medical sciences</subject><subject>Cells, Cultured</subject><subject>DNA, Viral - drug effects</subject><subject>DNA, Viral - genetics</subject><subject>Drug Resistance, Viral - drug effects</subject><subject>Drug Resistance, Viral - genetics</subject><subject>Genetic Variation</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - genetics</subject><subject>HIV Integrase - genetics</subject><subject>HIV Integrase Inhibitors - pharmacology</subject><subject>HIV-1 - drug effects</subject><subject>HIV-1 - genetics</subject><subject>Human immunodeficiency virus 1</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Immunodeficiencies</subject><subject>Immunodeficiencies. Immunoglobulinopathies</subject><subject>Immunopathology</subject><subject>Infectious diseases</subject><subject>Medical sciences</subject><subject>Mutation</subject><subject>Pharmacology. Drug treatments</subject><subject>Pyrrolidinones - pharmacology</subject><subject>Raltegravir Potassium</subject><subject>Sequence Analysis, DNA</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. Aids</subject><issn>0269-9370</issn><issn>1473-5571</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtvFDEQhC0EIkvgHyDkC-I0of2YsX0MGyCRIiEk4Dry2G1itDuzuL0Sy41_jiHLQ1w4dR--qm5VMfZYwJkAZ56_Pb84gwmEQiWtUiHJob_DVkIb1fW9EXfZCuTgOqcMnLAHRJ8AoAdr77MTCYM2DuyKfbu8-tAJTvupHnbIX3A_R77mea74sXhCjvPXwxaJ45ebPOXKY04JC841-w3f-VqxzMSXxAtSpurngLwufxnk-adwKdRWPuUl3OA2h6b2RP5AD9m95DeEj47zlL1_9fLd-rK7fvP6an1-3QUtdO2k80FqnYb2uVTBKa0iDJCk8i5G2YNwUUS02gmfht463weToo5uAoPSqVP27NZ3V5bPe6Q6bjMF3Gz8jMueRgtGWmvN_0mjrbOmWTZS35KhLEQF07greevLYRQw_mhpbC2N_7bUZE-OB_bTFuNv0a9aGvD0CHhqSaXSYs30h1NSSzMY9R0j-5yZ</recordid><startdate>20100910</startdate><enddate>20100910</enddate><creator>BAR-MAGEN, Tamara</creator><creator>DONAHUE, Daniel A</creator><creator>MCDONOUGH, Emily I</creator><creator>KUHL, Björn D</creator><creator>FALTENBACHER, Verena H</creator><creator>HONGTAO XU</creator><creator>MICHAUD, Veronique</creator><creator>SLOAN, Richard D</creator><creator>WAINBERG, Mark A</creator><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7T5</scope><scope>7U9</scope><scope>H94</scope></search><sort><creationdate>20100910</creationdate><title>HIV-1 subtype B and C integrase enzymes exhibit differential patterns of resistance to integrase inhibitors in biochemical assays</title><author>BAR-MAGEN, Tamara ; DONAHUE, Daniel A ; MCDONOUGH, Emily I ; KUHL, Björn D ; FALTENBACHER, Verena H ; HONGTAO XU ; MICHAUD, Veronique ; SLOAN, Richard D ; WAINBERG, Mark A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c414t-29ac244f664723c9343d060f23a9dd25019d1de8491af6589a5c7fd4d9b07e293</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>AIDS/HIV</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiviral agents</topic><topic>Biological and medical sciences</topic><topic>Cells, Cultured</topic><topic>DNA, Viral - drug effects</topic><topic>DNA, Viral - genetics</topic><topic>Drug Resistance, Viral - drug effects</topic><topic>Drug Resistance, Viral - genetics</topic><topic>Genetic Variation</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - genetics</topic><topic>HIV Integrase - genetics</topic><topic>HIV Integrase Inhibitors - pharmacology</topic><topic>HIV-1 - drug effects</topic><topic>HIV-1 - genetics</topic><topic>Human immunodeficiency virus 1</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Immunodeficiencies</topic><topic>Immunodeficiencies. Immunoglobulinopathies</topic><topic>Immunopathology</topic><topic>Infectious diseases</topic><topic>Medical sciences</topic><topic>Mutation</topic><topic>Pharmacology. Drug treatments</topic><topic>Pyrrolidinones - pharmacology</topic><topic>Raltegravir Potassium</topic><topic>Sequence Analysis, DNA</topic><topic>Viral diseases</topic><topic>Viral diseases of the lymphoid tissue and the blood. Aids</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>BAR-MAGEN, Tamara</creatorcontrib><creatorcontrib>DONAHUE, Daniel A</creatorcontrib><creatorcontrib>MCDONOUGH, Emily I</creatorcontrib><creatorcontrib>KUHL, Björn D</creatorcontrib><creatorcontrib>FALTENBACHER, Verena H</creatorcontrib><creatorcontrib>HONGTAO XU</creatorcontrib><creatorcontrib>MICHAUD, Veronique</creatorcontrib><creatorcontrib>SLOAN, Richard D</creatorcontrib><creatorcontrib>WAINBERG, Mark A</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>AIDS (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>BAR-MAGEN, Tamara</au><au>DONAHUE, Daniel A</au><au>MCDONOUGH, Emily I</au><au>KUHL, Björn D</au><au>FALTENBACHER, Verena H</au><au>HONGTAO XU</au><au>MICHAUD, Veronique</au><au>SLOAN, Richard D</au><au>WAINBERG, Mark A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HIV-1 subtype B and C integrase enzymes exhibit differential patterns of resistance to integrase inhibitors in biochemical assays</atitle><jtitle>AIDS (London)</jtitle><addtitle>AIDS</addtitle><date>2010-09-10</date><risdate>2010</risdate><volume>24</volume><issue>14</issue><spage>2171</spage><epage>2179</epage><pages>2171-2179</pages><issn>0269-9370</issn><eissn>1473-5571</eissn><abstract>Because of high intersubtype HIV-1 genetic variability, it has been shown that subtype-specific patterns of resistance to antiretroviral drugs exist. We wished to ascertain whether this might be true for integrase inhibitors.
We compared the susceptibility of subtype B and C HIV-1 integrase enzymes, harboring the previously reported resistance mutations E92Q, N155H, and E92Q/N155H, to clinically relevant integrase inhibitors. This was performed biochemically using a microtiter plate system.
Subtype C integrase enzymes bearing the resistance mutations E92Q/N155H were approximately 10-fold more susceptible to each of two integrase inhibitors, raltegravir and elvitegravir, than were subtype B recombinant integrase containing the same mutations.
Polymorphic differences within the subtype B and C integrase genes likely cause variations in the contribution of N155H alone or in combination with E92Q to drug resistance. It is possible that different viral subtypes may favor different mutational pathways, potentially leading to varying levels of drug resistance among different subtypes.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>20647908</pmid><doi>10.1097/QAD.0b013e32833cf265</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0269-9370 |
| ispartof | AIDS (London), 2010-09, Vol.24 (14), p.2171-2179 |
| issn | 0269-9370 1473-5571 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_807288879 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete |
| subjects | AIDS/HIV Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Biological and medical sciences Cells, Cultured DNA, Viral - drug effects DNA, Viral - genetics Drug Resistance, Viral - drug effects Drug Resistance, Viral - genetics Genetic Variation HIV Infections - drug therapy HIV Infections - genetics HIV Integrase - genetics HIV Integrase Inhibitors - pharmacology HIV-1 - drug effects HIV-1 - genetics Human immunodeficiency virus 1 Human viral diseases Humans Immunodeficiencies Immunodeficiencies. Immunoglobulinopathies Immunopathology Infectious diseases Medical sciences Mutation Pharmacology. Drug treatments Pyrrolidinones - pharmacology Raltegravir Potassium Sequence Analysis, DNA Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids |
| title | HIV-1 subtype B and C integrase enzymes exhibit differential patterns of resistance to integrase inhibitors in biochemical assays |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T15%3A35%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=HIV-1%20subtype%20B%20and%20C%20integrase%20enzymes%20exhibit%20differential%20patterns%20of%20resistance%20to%20integrase%20inhibitors%20in%20biochemical%20assays&rft.jtitle=AIDS%20(London)&rft.au=BAR-MAGEN,%20Tamara&rft.date=2010-09-10&rft.volume=24&rft.issue=14&rft.spage=2171&rft.epage=2179&rft.pages=2171-2179&rft.issn=0269-9370&rft.eissn=1473-5571&rft_id=info:doi/10.1097/QAD.0b013e32833cf265&rft_dat=%3Cproquest_cross%3E807288879%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=748987293&rft_id=info:pmid/20647908&rfr_iscdi=true |