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Búsqueda de mutaciones en el gen UL 97 asociadas a resistencia a ganciclovir en citomegalovirus obtenidos desde muestras biológicas de pacientes chilenos / Presence of mutations associated with ganciclovir resistance in cytomegalovirus UL 97 gene
Oyarzún, María Angélica; Bustos, Patricia; González, Marcela; Domínguez, María Isabel; Aguayo, Francisco; Nervi, Bruno; Ferres, Marcela.
  • Oyarzún, María Angélica; Pontificia Universidad Católica de Chile. Centro de Investigaciones Médicas. Departamento de Pediatría. CL
  • Bustos, Patricia; Pontificia Universidad Católica de Chile. Facultad de Medicina. Laboratorio de Infectología y Virología Molecular. CL
  • González, Marcela; Pontificia Universidad Católica de Chile. Centro de Investigaciones Médicas. Departamento de Pediatría. CL
  • Domínguez, María Isabel; Pontificia Universidad Católica de Chile. Facultad de Medicina. Departamento de Medicina Interna. CL
  • Aguayo, Francisco; Pontificia Universidad Católica de Chile. Centro de Investigaciones Médicas. Laboratorio de Patología Molecular y Epidemiología. CL
  • Nervi, Bruno; Pontificia Universidad Católica de Chile. Facultad de Medicina. Departamento de Oncología y Hematología. CL
  • Ferres, Marcela; Pontificia Universidad Católica de Chile. Facultad de Medicina. Departamento de Pediatría. CL
Rev. méd. Chile ; 138(4): 421-427, abr. 2010. ilus, tab
Article in Spanish | LILACS | ID: lil-553212
ABSTRACT

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.
Subject(s)

Full text: Available Index: LILACS (Americas) Main subject: Antiviral Agents / Ganciclovir / Phosphotransferases (Alcohol Group Acceptor) / Cytomegalovirus / Drug Resistance, Viral / Mutation Type of study: Risk factors Limits: Adolescent / Adult / Child / Child, preschool / Humans Country/Region as subject: South America / Chile Language: Spanish Journal: Rev. méd. Chile Journal subject: Medicine Year: 2010 Type: Article Affiliation country: Chile Institution/Affiliation country: Pontificia Universidad Católica de Chile/CL

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Full text: Available Index: LILACS (Americas) Main subject: Antiviral Agents / Ganciclovir / Phosphotransferases (Alcohol Group Acceptor) / Cytomegalovirus / Drug Resistance, Viral / Mutation Type of study: Risk factors Limits: Adolescent / Adult / Child / Child, preschool / Humans Country/Region as subject: South America / Chile Language: Spanish Journal: Rev. méd. Chile Journal subject: Medicine Year: 2010 Type: Article Affiliation country: Chile Institution/Affiliation country: Pontificia Universidad Católica de Chile/CL