Cytomegalovirus antiviral resistance associated with treatment induced UL97 (protein kinase) and UL54 (DNA polymerase) mutations
HCMV‐related illness due to infections with antiviral resistant virus was verified by phenotypic and genotypic assays in 17% (8/47) of high‐risk immunocompromised Australian patients. Selective PCR‐sequencing of UL97 (protein kinase; PK) and UL54 (DNA polymerase; DNApol) regions important for antivi...
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| Veröffentlicht in: | Journal of medical virology 2004-09, Vol.74 (1), p.85-93 |
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| creator | Scott, G.M. Isaacs, M.A. Zeng, F. Kesson, A.M. Rawlinson, W.D. |
| description | HCMV‐related illness due to infections with antiviral resistant virus was verified by phenotypic and genotypic assays in 17% (8/47) of high‐risk immunocompromised Australian patients. Selective PCR‐sequencing of UL97 (protein kinase; PK) and UL54 (DNA polymerase; DNApol) regions important for antiviral sensitivity, identified the majority (6/8) of resistant strains through detection of mutations known to confer antiviral resistance. Additionally, eight UL54 (DNApol) mutations (N408K, T691S, A692V, S695T, L737M, A834P, V955I, and A972V) of unknown phenotype were identified in six specimens from patients with clinical evidence of antiviral resistant infections. One isolate was resistant to ganciclovir (GCV) and another resistant to PFA on phenotypic testing where mutations in UL97 (PK) or UL54 (DNApol) were not detected, suggesting a loss of correlation between phenotype and genotype. Selective PCR‐sequencing of UL97 (PK) and UL54 (DNApol) provided rapid and comprehensive results, but missed some resistance detected by phenotypic assays. A combination of phenotypic and genotypic assays is recommended for complete analysis of CMV antiviral resistance, as well as further definition of the clinical relationship between novel UL54 (DNApol) mutations and antiviral resistance. J. Med. Virol. 74:85–93, 2004. © 2004 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/jmv.20150 |
| format | Article |
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Selective PCR‐sequencing of UL97 (protein kinase; PK) and UL54 (DNA polymerase; DNApol) regions important for antiviral sensitivity, identified the majority (6/8) of resistant strains through detection of mutations known to confer antiviral resistance. Additionally, eight UL54 (DNApol) mutations (N408K, T691S, A692V, S695T, L737M, A834P, V955I, and A972V) of unknown phenotype were identified in six specimens from patients with clinical evidence of antiviral resistant infections. One isolate was resistant to ganciclovir (GCV) and another resistant to PFA on phenotypic testing where mutations in UL97 (PK) or UL54 (DNApol) were not detected, suggesting a loss of correlation between phenotype and genotype. Selective PCR‐sequencing of UL97 (PK) and UL54 (DNApol) provided rapid and comprehensive results, but missed some resistance detected by phenotypic assays. A combination of phenotypic and genotypic assays is recommended for complete analysis of CMV antiviral resistance, as well as further definition of the clinical relationship between novel UL54 (DNApol) mutations and antiviral resistance. J. Med. Virol. 74:85–93, 2004. © 2004 Wiley‐Liss, Inc.</description><identifier>ISSN: 0146-6615</identifier><identifier>EISSN: 1096-9071</identifier><identifier>DOI: 10.1002/jmv.20150</identifier><identifier>PMID: 15258973</identifier><identifier>CODEN: JMVIDB</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Amino Acid Substitution ; Antiviral Agents - pharmacology ; Antiviral Agents - therapeutic use ; antivirals ; Australia ; Aziridines - pharmacology ; Biological and medical sciences ; CMV ; Cytomegalovirus ; Cytomegalovirus - drug effects ; Cytomegalovirus - genetics ; Cytomegalovirus - isolation & purification ; Cytomegalovirus Infections - drug therapy ; Cytomegalovirus Infections - virology ; DNA polymerase ; DNA, Viral - chemistry ; DNA, Viral - isolation & purification ; DNA-Directed DNA Polymerase - genetics ; DNA-Directed DNA Polymerase - physiology ; Drug Resistance, Viral - genetics ; Fundamental and applied biological sciences. Psychology ; Ganciclovir - pharmacology ; Genotype ; Human viral diseases ; Humans ; Immunocompromised Host ; Infectious diseases ; Medical sciences ; Microbiology ; Miscellaneous ; Molecular Sequence Data ; Mutation ; Phenotype ; Phosphotransferases (Alcohol Group Acceptor) - genetics ; Phosphotransferases (Alcohol Group Acceptor) - physiology ; resistance ; Sequence Analysis, DNA ; UL97 ; Viral diseases ; Viral Proteins - genetics ; Viral Proteins - physiology ; Virology</subject><ispartof>Journal of medical virology, 2004-09, Vol.74 (1), p.85-93</ispartof><rights>Copyright © 2004 Wiley‐Liss, Inc.</rights><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4200-944ec4cb5245cd2e9964e0ae89ea54d706172a3c0bc4384c592db42a1c393fed3</citedby><cites>FETCH-LOGICAL-c4200-944ec4cb5245cd2e9964e0ae89ea54d706172a3c0bc4384c592db42a1c393fed3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjmv.20150$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjmv.20150$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15964335$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15258973$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Scott, G.M.</creatorcontrib><creatorcontrib>Isaacs, M.A.</creatorcontrib><creatorcontrib>Zeng, F.</creatorcontrib><creatorcontrib>Kesson, A.M.</creatorcontrib><creatorcontrib>Rawlinson, W.D.</creatorcontrib><title>Cytomegalovirus antiviral resistance associated with treatment induced UL97 (protein kinase) and UL54 (DNA polymerase) mutations</title><title>Journal of medical virology</title><addtitle>J. Med. Virol</addtitle><description>HCMV‐related illness due to infections with antiviral resistant virus was verified by phenotypic and genotypic assays in 17% (8/47) of high‐risk immunocompromised Australian patients. Selective PCR‐sequencing of UL97 (protein kinase; PK) and UL54 (DNA polymerase; DNApol) regions important for antiviral sensitivity, identified the majority (6/8) of resistant strains through detection of mutations known to confer antiviral resistance. Additionally, eight UL54 (DNApol) mutations (N408K, T691S, A692V, S695T, L737M, A834P, V955I, and A972V) of unknown phenotype were identified in six specimens from patients with clinical evidence of antiviral resistant infections. One isolate was resistant to ganciclovir (GCV) and another resistant to PFA on phenotypic testing where mutations in UL97 (PK) or UL54 (DNApol) were not detected, suggesting a loss of correlation between phenotype and genotype. Selective PCR‐sequencing of UL97 (PK) and UL54 (DNApol) provided rapid and comprehensive results, but missed some resistance detected by phenotypic assays. A combination of phenotypic and genotypic assays is recommended for complete analysis of CMV antiviral resistance, as well as further definition of the clinical relationship between novel UL54 (DNApol) mutations and antiviral resistance. J. Med. Virol. 74:85–93, 2004. © 2004 Wiley‐Liss, Inc.</description><subject>Amino Acid Substitution</subject><subject>Antiviral Agents - pharmacology</subject><subject>Antiviral Agents - therapeutic use</subject><subject>antivirals</subject><subject>Australia</subject><subject>Aziridines - pharmacology</subject><subject>Biological and medical sciences</subject><subject>CMV</subject><subject>Cytomegalovirus</subject><subject>Cytomegalovirus - drug effects</subject><subject>Cytomegalovirus - genetics</subject><subject>Cytomegalovirus - isolation & purification</subject><subject>Cytomegalovirus Infections - drug therapy</subject><subject>Cytomegalovirus Infections - virology</subject><subject>DNA polymerase</subject><subject>DNA, Viral - chemistry</subject><subject>DNA, Viral - isolation & purification</subject><subject>DNA-Directed DNA Polymerase - genetics</subject><subject>DNA-Directed DNA Polymerase - physiology</subject><subject>Drug Resistance, Viral - genetics</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Ganciclovir - pharmacology</subject><subject>Genotype</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Immunocompromised Host</subject><subject>Infectious diseases</subject><subject>Medical sciences</subject><subject>Microbiology</subject><subject>Miscellaneous</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>Phenotype</subject><subject>Phosphotransferases (Alcohol Group Acceptor) - genetics</subject><subject>Phosphotransferases (Alcohol Group Acceptor) - physiology</subject><subject>resistance</subject><subject>Sequence Analysis, DNA</subject><subject>UL97</subject><subject>Viral diseases</subject><subject>Viral Proteins - genetics</subject><subject>Viral Proteins - physiology</subject><subject>Virology</subject><issn>0146-6615</issn><issn>1096-9071</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkTtzEzEURjUMDDGBgj_AqIFJik301qoMBvIYYxoCpUbWXoOSfTiSNsEdPx05doCGoZJG99zvSjoIvaTkiBLCjq-62yNGqCSP0IQSoypDNH2MJoQKVSlF5R56ltIVIaQ2jD1Fe1QyWRvNJ-jndJ2HDr65drgNcUzY9TmUnWtxhBRSdr0H7FIafHAZGnwX8necI7jcQZ9x6JvRl-PLmdH4YBWHDKHH16F3CQ5L2KYiBT54Nz_Bq6FddxDvK92YXQ5Dn56jJ0vXJnixW_fR5Yf3n6dn1ezT6fn0ZFZ5wQipjBDghV9IJqRvGBijBBAHtQEnRaOJopo57snCC14LLw1rFoI56rnhS2j4PnqzzS13vBkhZduF5KFtXQ_DmKxSmtamZv8FaU2kYHIDHm5BH4eUIiztKobOxbWlxG682OLF3nsp7Ktd6LjooPlD7kQU4PUOcMm7dhnLv4f0F1fey7ks3PGWuwstrP890V58_PIwutp2FJnw43eHi9dWaa6l_To_texCq3ltzuxb_gsITbPD</recordid><startdate>200409</startdate><enddate>200409</enddate><creator>Scott, G.M.</creator><creator>Isaacs, M.A.</creator><creator>Zeng, F.</creator><creator>Kesson, A.M.</creator><creator>Rawlinson, W.D.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Liss</general><scope>BSCLL</scope><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>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>200409</creationdate><title>Cytomegalovirus antiviral resistance associated with treatment induced UL97 (protein kinase) and UL54 (DNA polymerase) mutations</title><author>Scott, G.M. ; Isaacs, M.A. ; Zeng, F. ; Kesson, A.M. ; Rawlinson, W.D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4200-944ec4cb5245cd2e9964e0ae89ea54d706172a3c0bc4384c592db42a1c393fed3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Amino Acid Substitution</topic><topic>Antiviral Agents - pharmacology</topic><topic>Antiviral Agents - therapeutic use</topic><topic>antivirals</topic><topic>Australia</topic><topic>Aziridines - pharmacology</topic><topic>Biological and medical sciences</topic><topic>CMV</topic><topic>Cytomegalovirus</topic><topic>Cytomegalovirus - drug effects</topic><topic>Cytomegalovirus - genetics</topic><topic>Cytomegalovirus - isolation & purification</topic><topic>Cytomegalovirus Infections - drug therapy</topic><topic>Cytomegalovirus Infections - virology</topic><topic>DNA polymerase</topic><topic>DNA, Viral - chemistry</topic><topic>DNA, Viral - isolation & purification</topic><topic>DNA-Directed DNA Polymerase - genetics</topic><topic>DNA-Directed DNA Polymerase - physiology</topic><topic>Drug Resistance, Viral - genetics</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Ganciclovir - pharmacology</topic><topic>Genotype</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Immunocompromised Host</topic><topic>Infectious diseases</topic><topic>Medical sciences</topic><topic>Microbiology</topic><topic>Miscellaneous</topic><topic>Molecular Sequence Data</topic><topic>Mutation</topic><topic>Phenotype</topic><topic>Phosphotransferases (Alcohol Group Acceptor) - genetics</topic><topic>Phosphotransferases (Alcohol Group Acceptor) - physiology</topic><topic>resistance</topic><topic>Sequence Analysis, DNA</topic><topic>UL97</topic><topic>Viral diseases</topic><topic>Viral Proteins - genetics</topic><topic>Viral Proteins - physiology</topic><topic>Virology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Scott, G.M.</creatorcontrib><creatorcontrib>Isaacs, M.A.</creatorcontrib><creatorcontrib>Zeng, F.</creatorcontrib><creatorcontrib>Kesson, A.M.</creatorcontrib><creatorcontrib>Rawlinson, W.D.</creatorcontrib><collection>Istex</collection><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>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of medical virology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Scott, G.M.</au><au>Isaacs, M.A.</au><au>Zeng, F.</au><au>Kesson, A.M.</au><au>Rawlinson, W.D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytomegalovirus antiviral resistance associated with treatment induced UL97 (protein kinase) and UL54 (DNA polymerase) mutations</atitle><jtitle>Journal of medical virology</jtitle><addtitle>J. Med. Virol</addtitle><date>2004-09</date><risdate>2004</risdate><volume>74</volume><issue>1</issue><spage>85</spage><epage>93</epage><pages>85-93</pages><issn>0146-6615</issn><eissn>1096-9071</eissn><coden>JMVIDB</coden><abstract>HCMV‐related illness due to infections with antiviral resistant virus was verified by phenotypic and genotypic assays in 17% (8/47) of high‐risk immunocompromised Australian patients. Selective PCR‐sequencing of UL97 (protein kinase; PK) and UL54 (DNA polymerase; DNApol) regions important for antiviral sensitivity, identified the majority (6/8) of resistant strains through detection of mutations known to confer antiviral resistance. Additionally, eight UL54 (DNApol) mutations (N408K, T691S, A692V, S695T, L737M, A834P, V955I, and A972V) of unknown phenotype were identified in six specimens from patients with clinical evidence of antiviral resistant infections. One isolate was resistant to ganciclovir (GCV) and another resistant to PFA on phenotypic testing where mutations in UL97 (PK) or UL54 (DNApol) were not detected, suggesting a loss of correlation between phenotype and genotype. Selective PCR‐sequencing of UL97 (PK) and UL54 (DNApol) provided rapid and comprehensive results, but missed some resistance detected by phenotypic assays. A combination of phenotypic and genotypic assays is recommended for complete analysis of CMV antiviral resistance, as well as further definition of the clinical relationship between novel UL54 (DNApol) mutations and antiviral resistance. J. Med. Virol. 74:85–93, 2004. © 2004 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>15258973</pmid><doi>10.1002/jmv.20150</doi><tpages>9</tpages></addata></record> |
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| subjects | Amino Acid Substitution Antiviral Agents - pharmacology Antiviral Agents - therapeutic use antivirals Australia Aziridines - pharmacology Biological and medical sciences CMV Cytomegalovirus Cytomegalovirus - drug effects Cytomegalovirus - genetics Cytomegalovirus - isolation & purification Cytomegalovirus Infections - drug therapy Cytomegalovirus Infections - virology DNA polymerase DNA, Viral - chemistry DNA, Viral - isolation & purification DNA-Directed DNA Polymerase - genetics DNA-Directed DNA Polymerase - physiology Drug Resistance, Viral - genetics Fundamental and applied biological sciences. Psychology Ganciclovir - pharmacology Genotype Human viral diseases Humans Immunocompromised Host Infectious diseases Medical sciences Microbiology Miscellaneous Molecular Sequence Data Mutation Phenotype Phosphotransferases (Alcohol Group Acceptor) - genetics Phosphotransferases (Alcohol Group Acceptor) - physiology resistance Sequence Analysis, DNA UL97 Viral diseases Viral Proteins - genetics Viral Proteins - physiology Virology |
| title | Cytomegalovirus antiviral resistance associated with treatment induced UL97 (protein kinase) and UL54 (DNA polymerase) mutations |
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