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De Novo Genotypic Heterogeneity in the UL56 Region in Cytomegalovirus-Infected Tissues: Implications for Primary Letermovir Resistance

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dc.contributor.author이경화-
dc.contributor.author한상훈-
dc.contributor.author임범진-
dc.date.accessioned2020-09-28T10:36:20Z-
dc.date.available2020-09-28T10:36:20Z-
dc.date.issued2020-04-
dc.identifier.issn0022-1899-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/179158-
dc.description.abstractBackground: Letermovir, an inhibitor of unique long (UL)56-encoded cytomegalovirus (CMV)-terminase, shows prophylactic effects with low-grade adverse events in hematopoietic stem cell transplant recipients. Despite few case reports on acquired letermovir resistance, the frequency of de novo amino acid (A.A.) changes encoded by UL56 in CMV-infected tissues is unclear. Methods: We analyzed CMV UL56 sequences between the conserved region IV and variable region I in 175 formalin-fixed, paraffin-embedded tissues obtained from 147 patients showing positive CMV immunochemical staining between November 2012 and October 2016. Nucleotides 552-1330 of the open reading frame of UL56 were amplified with 5 primers and sequenced by a dideoxy fluorescence-based cycle. Results: Six (3.4%) tissues from 4 (2.7%) patients harbored A.A. substitutions. There were no known potent resistant mutations. However, we found C325Y in 2 tissues from 1 patient, along with other mutations. Four novel A.A. changes, which have not been observed in previous in vitro experiments, were identified (T244I, S301T, G312V, and M434I). Most (9 of 11, 81.8%) of the A.A. changes occurred between the codons 301 and 325 present between the conserved regions V and VI. Conclusions: The treatment difficulties associated with letermovir resistance in a clinical setting need to be verified before its widespread use.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherOxford University Press-
dc.relation.isPartOfJOURNAL OF INFECTIOUS DISEASES-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.titleDe Novo Genotypic Heterogeneity in the UL56 Region in Cytomegalovirus-Infected Tissues: Implications for Primary Letermovir Resistance-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학교실)-
dc.contributor.googleauthorHorim Jo-
dc.contributor.googleauthorDa Eun Kwon-
dc.contributor.googleauthorSang Hoon Han-
dc.contributor.googleauthorSeo Yeon Min-
dc.contributor.googleauthorYeon-Mi Hong-
dc.contributor.googleauthorBeom Jin Lim-
dc.contributor.googleauthorKyoung Hwa Lee-
dc.contributor.googleauthorJeong-Hyeon Jo-
dc.identifier.doi10.1093/infdis/jiz642-
dc.contributor.localIdA04620-
dc.contributor.localIdA04286-
dc.contributor.localIdA04286-
dc.contributor.localIdA03363-
dc.contributor.localIdA03363-
dc.relation.journalcodeJ01454-
dc.identifier.eissn1537-6613-
dc.identifier.pmid31802131-
dc.identifier.urlhttps://academic.oup.com/jid/article/221/9/1480/5658434-
dc.subject.keywordcytomegalovirus-
dc.subject.keywordgenotype-
dc.subject.keywordletermovir-
dc.subject.keywordresistance-
dc.subject.keywordtissues-
dc.contributor.alternativeNameLee, Kyoung Hwa-
dc.contributor.affiliatedAuthor이경화-
dc.contributor.affiliatedAuthor한상훈-
dc.contributor.affiliatedAuthor한상훈-
dc.contributor.affiliatedAuthor임범진-
dc.contributor.affiliatedAuthor임범진-
dc.citation.volume221-
dc.citation.number9-
dc.citation.startPage1480-
dc.citation.endPage1487-
dc.identifier.bibliographicCitationJOURNAL OF INFECTIOUS DISEASES, Vol.221(9) : 1480-1487, 2020-04-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers

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