Biochemical Characterization of a Virus Isolate, Recovered from a Patient with Herpes Keratitis, That Was Clinically Resistant to Acyclovir
In vitro susceptibility assays of herpes simplex virus (HSV) do not necessarily correlate with treatment outcome. An HSV type 1 (HSV-1) isolate, N4, recovered from a patient who presented with herpes keratitis with localized immunosuppression, was characterized for susceptibility. Although the 50% i...
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| Veröffentlicht in: | Clinical infectious diseases 2001-12, Vol.33 (12), p.2034-2039 |
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| creator | Sarisky, Robert T. Cano, Rachel Nguyen, Tammy T. Wittrock, Robert J. Duffy, Karen E. Clark, Phil Bartus, Joan O. Bacon, Teresa H. Caspers-Velu, Laure Hodinka, Richard L. Leary, Jeffry J. |
| description | In vitro susceptibility assays of herpes simplex virus (HSV) do not necessarily correlate with treatment outcome. An HSV type 1 (HSV-1) isolate, N4, recovered from a patient who presented with herpes keratitis with localized immunosuppression, was characterized for susceptibility. Although the 50% inhibitory concentration (IC50) for this isolate was less than the accepted breakpoint for defining resistance to acyclovir (>2.0 µg/mL), the following lines of evidence suggest that the isolate was acyclovir resistant: (1) the clinical history confirmed that the infection was nonresponsive to acyclovir; (2) the in vitro susceptibility was similar to that of a thymidine kinase (TK)-negative, acyclovir-resistant virus SLU360; (3) the IC50 of acyclovir was more than 10 times the IC50 for an acyclovir-susceptible control strain; (4) plaque-purified clonal isolates were resistant to acyclovir (IC50s, >2.0 µg/mL); and (5) biochemical studies indicated that the HSV-1 N4 TK was partially impaired for acyclovir phosphorylation. Although residue changes were found in both the viral tk and pol coding regions of HSV-1 N4, characterization of a recombinant virus expressing the HSV-1 N4 polymerase suggested that the TK and Pol together conferred the acyclovir-resistance phenotype. |
| doi_str_mv | 10.1086/338046 |
| format | Article |
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An HSV type 1 (HSV-1) isolate, N4, recovered from a patient who presented with herpes keratitis with localized immunosuppression, was characterized for susceptibility. Although the 50% inhibitory concentration (IC50) for this isolate was less than the accepted breakpoint for defining resistance to acyclovir (>2.0 µg/mL), the following lines of evidence suggest that the isolate was acyclovir resistant: (1) the clinical history confirmed that the infection was nonresponsive to acyclovir; (2) the in vitro susceptibility was similar to that of a thymidine kinase (TK)-negative, acyclovir-resistant virus SLU360; (3) the IC50 of acyclovir was more than 10 times the IC50 for an acyclovir-susceptible control strain; (4) plaque-purified clonal isolates were resistant to acyclovir (IC50s, >2.0 µg/mL); and (5) biochemical studies indicated that the HSV-1 N4 TK was partially impaired for acyclovir phosphorylation. Although residue changes were found in both the viral tk and pol coding regions of HSV-1 N4, characterization of a recombinant virus expressing the HSV-1 N4 polymerase suggested that the TK and Pol together conferred the acyclovir-resistance phenotype.</description><identifier>ISSN: 1058-4838</identifier><identifier>EISSN: 1537-6591</identifier><identifier>DOI: 10.1086/338046</identifier><identifier>PMID: 11712095</identifier><identifier>CODEN: CIDIEL</identifier><language>eng</language><publisher>Chicago, IL: The University of Chicago Press</publisher><subject>Acyclovir - pharmacology ; Aged ; Antibiotics. Antiinfectious agents. 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An HSV type 1 (HSV-1) isolate, N4, recovered from a patient who presented with herpes keratitis with localized immunosuppression, was characterized for susceptibility. Although the 50% inhibitory concentration (IC50) for this isolate was less than the accepted breakpoint for defining resistance to acyclovir (>2.0 µg/mL), the following lines of evidence suggest that the isolate was acyclovir resistant: (1) the clinical history confirmed that the infection was nonresponsive to acyclovir; (2) the in vitro susceptibility was similar to that of a thymidine kinase (TK)-negative, acyclovir-resistant virus SLU360; (3) the IC50 of acyclovir was more than 10 times the IC50 for an acyclovir-susceptible control strain; (4) plaque-purified clonal isolates were resistant to acyclovir (IC50s, >2.0 µg/mL); and (5) biochemical studies indicated that the HSV-1 N4 TK was partially impaired for acyclovir phosphorylation. 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Antiparasitic agents</subject><subject>Antiviral agents</subject><subject>Antiviral Agents - pharmacology</subject><subject>Antivirals</subject><subject>Biochemistry</subject><subject>Biological and medical sciences</subject><subject>Cell lines</subject><subject>DNA</subject><subject>Drug Resistance, Microbial</subject><subject>Herpes Simplex - virology</subject><subject>Herpesvirus 1, Human - drug effects</subject><subject>Herpesvirus 1, Human - isolation & purification</subject><subject>Human herpesvirus 1</subject><subject>Humans</subject><subject>Infections</subject><subject>Inhibitory concentration 50</subject><subject>Keratitis - virology</subject><subject>Major Articles</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microbial Sensitivity Tests</subject><subject>Pharmacology. Drug treatments</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>Simplexvirus</subject><subject>Viruses</subject><issn>1058-4838</issn><issn>1537-6591</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu1DAQhiMEoqXAEyBkDnBqwI7txDmWFWUrClSoQMXFmnXGWrdJvNhOYXkFXhqXXXVPiINla_7P_2jmL4rHjL5kVNWvOFdU1HeKfSZ5U9ayZXfzm0pVCsXVXvEgxktKGVNU3i_2GGtYRVu5X_x-7bxZ4uAM9GS2hAAmYXC_IDk_Em8JkC8uTJGcRN9DwkPyCY2_xoAdscEPWT_LLI6J_HBpSeYYVhjJOwy5mlw8JOdLSOQrRDLr3XjTpl9nj-higvwpeXJk1qb31y48LO5Z6CM-2t4HxefjN-ezeXn68e3J7Oi0NELyVLaiWUhlW9p1qkGJQuRhFAdrKw4S0IAFwTjwFrt8wFbNojOVrBivayMNPyhebHxXwX-fMCY9uGiw72FEP0XdVJVqWsb-CzIl6jbvewea4GMMaPUquAHCWjOqb_LRm3wy-HTrOC0G7HbYNpAMPN8CEPOubIDRuLjjOG-54DRzzzacn1b_bvZkw1zG5MMtJYSq2r9yuZFzFPjzVoZwpeuGN1LPL77ps4vjirH3H7TifwA-rLrW</recordid><startdate>20011215</startdate><enddate>20011215</enddate><creator>Sarisky, Robert T.</creator><creator>Cano, Rachel</creator><creator>Nguyen, Tammy T.</creator><creator>Wittrock, Robert J.</creator><creator>Duffy, Karen E.</creator><creator>Clark, Phil</creator><creator>Bartus, Joan O.</creator><creator>Bacon, Teresa H.</creator><creator>Caspers-Velu, Laure</creator><creator>Hodinka, Richard L.</creator><creator>Leary, Jeffry J.</creator><general>The University of Chicago Press</general><general>University of Chicago Press</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>20011215</creationdate><title>Biochemical Characterization of a Virus Isolate, Recovered from a Patient with Herpes Keratitis, That Was Clinically Resistant to Acyclovir</title><author>Sarisky, Robert T. ; Cano, Rachel ; Nguyen, Tammy T. ; Wittrock, Robert J. ; Duffy, Karen E. ; Clark, Phil ; Bartus, Joan O. ; Bacon, Teresa H. ; Caspers-Velu, Laure ; Hodinka, Richard L. ; Leary, Jeffry J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c453t-947b58f90dd87e5e4471283aff23a5aecafa413a39ed39eaf27bdc2521366c5c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Acyclovir - pharmacology</topic><topic>Aged</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiviral agents</topic><topic>Antiviral Agents - pharmacology</topic><topic>Antivirals</topic><topic>Biochemistry</topic><topic>Biological and medical sciences</topic><topic>Cell lines</topic><topic>DNA</topic><topic>Drug Resistance, Microbial</topic><topic>Herpes Simplex - virology</topic><topic>Herpesvirus 1, Human - drug effects</topic><topic>Herpesvirus 1, Human - isolation & purification</topic><topic>Human herpesvirus 1</topic><topic>Humans</topic><topic>Infections</topic><topic>Inhibitory concentration 50</topic><topic>Keratitis - virology</topic><topic>Major Articles</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microbial Sensitivity Tests</topic><topic>Pharmacology. 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An HSV type 1 (HSV-1) isolate, N4, recovered from a patient who presented with herpes keratitis with localized immunosuppression, was characterized for susceptibility. Although the 50% inhibitory concentration (IC50) for this isolate was less than the accepted breakpoint for defining resistance to acyclovir (>2.0 µg/mL), the following lines of evidence suggest that the isolate was acyclovir resistant: (1) the clinical history confirmed that the infection was nonresponsive to acyclovir; (2) the in vitro susceptibility was similar to that of a thymidine kinase (TK)-negative, acyclovir-resistant virus SLU360; (3) the IC50 of acyclovir was more than 10 times the IC50 for an acyclovir-susceptible control strain; (4) plaque-purified clonal isolates were resistant to acyclovir (IC50s, >2.0 µg/mL); and (5) biochemical studies indicated that the HSV-1 N4 TK was partially impaired for acyclovir phosphorylation. Although residue changes were found in both the viral tk and pol coding regions of HSV-1 N4, characterization of a recombinant virus expressing the HSV-1 N4 polymerase suggested that the TK and Pol together conferred the acyclovir-resistance phenotype.</abstract><cop>Chicago, IL</cop><pub>The University of Chicago Press</pub><pmid>11712095</pmid><doi>10.1086/338046</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | Jstor Complete Legacy; Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Acyclovir - pharmacology Aged Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Antiviral Agents - pharmacology Antivirals Biochemistry Biological and medical sciences Cell lines DNA Drug Resistance, Microbial Herpes Simplex - virology Herpesvirus 1, Human - drug effects Herpesvirus 1, Human - isolation & purification Human herpesvirus 1 Humans Infections Inhibitory concentration 50 Keratitis - virology Major Articles Male Medical sciences Microbial Sensitivity Tests Pharmacology. Drug treatments Phenotype Phenotypes Simplexvirus Viruses |
| title | Biochemical Characterization of a Virus Isolate, Recovered from a Patient with Herpes Keratitis, That Was Clinically Resistant to Acyclovir |
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