Búsqueda de mutaciones en el gen UL 97 asociadas a resistencia a ganciclovir en citomegalovirus obtenidos desde muestras biológicas de pacientes chilenos

Background: Long term use of ganciclovir (GCV) is associated with acquired resistance to it. Ninety percent of the responsible mutations occur in cytomegalovirus (CMV) UL 97 gene. Aim: To search for these mutations, comparing nucleotide sequences of CMV-positive samples from post transplant and immunocompromised patients receiving GCV, with sequences of CMV isolates obtained from subjects not exposed to the drug. Patients and Methods: Codons 440 to 465 of gene UL 97, in-cluding the most common mutations causing resistance to GCV, were amplifed in 33 plasma samples from patients exposed to GCV and in 15 urine samples of newborns. Both populations and their nucleotide sequences were compared with the prototype strain CMV AD169. Results: Samples of exposed patients had multiple mutations but only one had a mutation associated with clinical resistance (M460I). Eight subjects had the D605E mutation, whose role in resistance is controversial. The remaining 150 mutations were silent mutations. Conclusions: A low frequency of mutations associated with CMV resistance to GCV was found in these exposed and unexposed samples. These mutations may refect coexistence of multiple genetic variants of CMV. The absence of clinical expression of resistance, even with these mutations, can be explained by the use of GCV for a shorter lapse than that associated with the appearance of resistance.

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Main Authors: OYARZÚN,MARÍA ANGÉLICA, BUSTOS,PATRICIA, GONZÁLEZ,MARCELA, DOMÍNGUEZ,MARÍA ISABEL, AGUAYO,FRANCISCO, NERVI,BRUNO, FERRES,MARCELA
Format: Digital revista
Language:Spanish / Castilian
Published: Sociedad Médica de Santiago 2010
Online Access:http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0034-98872010000400005
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spelling oai:scielo:S0034-988720100004000052010-06-30Búsqueda de mutaciones en el gen UL 97 asociadas a resistencia a ganciclovir en citomegalovirus obtenidos desde muestras biológicas de pacientes chilenosOYARZÚN,MARÍA ANGÉLICABUSTOS,PATRICIAGONZÁLEZ,MARCELADOMÍNGUEZ,MARÍA ISABELAGUAYO,FRANCISCONERVI,BRUNOFERRES,MARCELA Anti viral drug resistance Cytomegalovirus Ganciclovir Background: Long term use of ganciclovir (GCV) is associated with acquired resistance to it. Ninety percent of the responsible mutations occur in cytomegalovirus (CMV) UL 97 gene. Aim: To search for these mutations, comparing nucleotide sequences of CMV-positive samples from post transplant and immunocompromised patients receiving GCV, with sequences of CMV isolates obtained from subjects not exposed to the drug. Patients and Methods: Codons 440 to 465 of gene UL 97, in-cluding the most common mutations causing resistance to GCV, were amplifed in 33 plasma samples from patients exposed to GCV and in 15 urine samples of newborns. Both populations and their nucleotide sequences were compared with the prototype strain CMV AD169. Results: Samples of exposed patients had multiple mutations but only one had a mutation associated with clinical resistance (M460I). Eight subjects had the D605E mutation, whose role in resistance is controversial. The remaining 150 mutations were silent mutations. Conclusions: A low frequency of mutations associated with CMV resistance to GCV was found in these exposed and unexposed samples. These mutations may refect coexistence of multiple genetic variants of CMV. The absence of clinical expression of resistance, even with these mutations, can be explained by the use of GCV for a shorter lapse than that associated with the appearance of resistance.info:eu-repo/semantics/openAccessSociedad Médica de SantiagoRevista médica de Chile v.138 n.4 20102010-04-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0034-98872010000400005es10.4067/S0034-98872010000400005
institution SCIELO
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country Chile
countrycode CL
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libraryname SciELO
language Spanish / Castilian
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author OYARZÚN,MARÍA ANGÉLICA
BUSTOS,PATRICIA
GONZÁLEZ,MARCELA
DOMÍNGUEZ,MARÍA ISABEL
AGUAYO,FRANCISCO
NERVI,BRUNO
FERRES,MARCELA
spellingShingle OYARZÚN,MARÍA ANGÉLICA
BUSTOS,PATRICIA
GONZÁLEZ,MARCELA
DOMÍNGUEZ,MARÍA ISABEL
AGUAYO,FRANCISCO
NERVI,BRUNO
FERRES,MARCELA
Búsqueda de mutaciones en el gen UL 97 asociadas a resistencia a ganciclovir en citomegalovirus obtenidos desde muestras biológicas de pacientes chilenos
author_facet OYARZÚN,MARÍA ANGÉLICA
BUSTOS,PATRICIA
GONZÁLEZ,MARCELA
DOMÍNGUEZ,MARÍA ISABEL
AGUAYO,FRANCISCO
NERVI,BRUNO
FERRES,MARCELA
author_sort OYARZÚN,MARÍA ANGÉLICA
title Búsqueda de mutaciones en el gen UL 97 asociadas a resistencia a ganciclovir en citomegalovirus obtenidos desde muestras biológicas de pacientes chilenos
title_short Búsqueda de mutaciones en el gen UL 97 asociadas a resistencia a ganciclovir en citomegalovirus obtenidos desde muestras biológicas de pacientes chilenos
title_full Búsqueda de mutaciones en el gen UL 97 asociadas a resistencia a ganciclovir en citomegalovirus obtenidos desde muestras biológicas de pacientes chilenos
title_fullStr Búsqueda de mutaciones en el gen UL 97 asociadas a resistencia a ganciclovir en citomegalovirus obtenidos desde muestras biológicas de pacientes chilenos
title_full_unstemmed Búsqueda de mutaciones en el gen UL 97 asociadas a resistencia a ganciclovir en citomegalovirus obtenidos desde muestras biológicas de pacientes chilenos
title_sort búsqueda de mutaciones en el gen ul 97 asociadas a resistencia a ganciclovir en citomegalovirus obtenidos desde muestras biológicas de pacientes chilenos
description Background: Long term use of ganciclovir (GCV) is associated with acquired resistance to it. Ninety percent of the responsible mutations occur in cytomegalovirus (CMV) UL 97 gene. Aim: To search for these mutations, comparing nucleotide sequences of CMV-positive samples from post transplant and immunocompromised patients receiving GCV, with sequences of CMV isolates obtained from subjects not exposed to the drug. Patients and Methods: Codons 440 to 465 of gene UL 97, in-cluding the most common mutations causing resistance to GCV, were amplifed in 33 plasma samples from patients exposed to GCV and in 15 urine samples of newborns. Both populations and their nucleotide sequences were compared with the prototype strain CMV AD169. Results: Samples of exposed patients had multiple mutations but only one had a mutation associated with clinical resistance (M460I). Eight subjects had the D605E mutation, whose role in resistance is controversial. The remaining 150 mutations were silent mutations. Conclusions: A low frequency of mutations associated with CMV resistance to GCV was found in these exposed and unexposed samples. These mutations may refect coexistence of multiple genetic variants of CMV. The absence of clinical expression of resistance, even with these mutations, can be explained by the use of GCV for a shorter lapse than that associated with the appearance of resistance.
publisher Sociedad Médica de Santiago
publishDate 2010
url http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0034-98872010000400005
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