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Basic Characteristics of Mutations
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Mutation Site
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P522S |
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Mutation Site Sentence
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Further ganciclovir treatment induced a new mutation in both UL97 (H520Q) and UL54 (P522S) with final emergence of double resistance to both ganciclovir and cidofovir. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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UL54 |
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Standardized Encoding Gene
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UL54
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Cytomegalovirus infections
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Immune
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Y |
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Target Gene
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CD4
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Clinical and Epidemiological Correlations
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Clinical Information
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Y |
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Treatment
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ganciclovir;cidofovir |
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Location
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- |
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Literature Information
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PMID
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14739146
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Title
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Human cytomegalovirus double resistance in a donor-positive/recipient-negative lung transplant patient with an impaired CD4-mediated specific immune response
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Author
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Baldanti F,Lilleri D,Campanini G,Comolli G,Ridolfo AL,Rusconi S,Gerna G
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Journal
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The Journal of antimicrobial chemotherapy
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Journal Info
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2004 Mar;53(3):536-9
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Abstract
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BACKGROUND: Emergence of human cytomegalovirus (HCMV) resistance to ganciclovir in solid-organ transplant recipients has been found to be mostly associated with primary HCMV infection. MATERIALS AND METHODS: The case of a donor-positive/recipient-negative (D(+)/R(-)) lung transplant patient developing ganciclovir and cidofovir resistance is described. HCMV infection was monitored by weekly determination of antigenaemia, viraemia and DNAaemia. HCMV-specific CD4 cell immunity was determined by cytokine flow cytometry. The emergence of drug-resistant HCMV strains was documented by sequencing of UL97 and UL54 genes of HCMV directly in blood samples. RESULTS: Following primary HCMV infection, the patient showed repeated reactivations for over a year, eventually resulting in the selection of a ganciclovir-resistant HCMV strain with a mutation in the UL97 gene product (A594V). Determination of HCMV-specific CD4 cell immunity showed a persistently impaired immune response. Subsequent foscarnet treatment allowed only transitory virus clearance from blood owing to renal toxicity. Further ganciclovir treatment induced a new mutation in both UL97 (H520Q) and UL54 (P522S) with final emergence of double resistance to both ganciclovir and cidofovir. The patient eventually died of lung failure. DISCUSSION: Determination of HCMV-specific CD4 cell immunity could be of help in predicting the emergence of drug-resistant strains in D(+)/R(-) transplant recipients.
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Sequence Data
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-
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