Cytomegalovirus UL97 kinase mutations that confer maribavir resistance

Sunwen Chou, Laura C. Van Wechel, Gail I. Marousek

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

The cytomegalovirus (CMV) UL97 kinase inhibitor maribavir (MBV) is undergoing clinical antiviral trials. Two clinical CMV isolates serially passaged in cell culture under MBV showed >20-fold increases in MBV resistance after the development of the UL97 mutation V353A in one of the isolates and of T409M in the other. Marker transfer studies confirmed that the V353A and T409M mutations conferred ∼15-fold and ∼80-fold increases, respectively, in MBV resistance without significantly affecting ganciclovir susceptibility. The 3 UL97 mutations now known to confer MBV resistance are located upstream of UL97 mutations linked to ganciclovir resistance, closer to kinase domains that are associated with adenosine triphosphate binding and phosphotransfer.

Original languageEnglish (US)
Pages (from-to)91-94
Number of pages4
JournalJournal of Infectious Diseases
Volume196
Issue number1
DOIs
StatePublished - Jul 1 2007

Fingerprint

Cytomegalovirus
Phosphotransferases
Mutation
Ganciclovir
Antiviral Agents
Cell Culture Techniques
Adenosine Triphosphate
maribavir
Clinical Trials

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Cytomegalovirus UL97 kinase mutations that confer maribavir resistance. / Chou, Sunwen; Van Wechel, Laura C.; Marousek, Gail I.

In: Journal of Infectious Diseases, Vol. 196, No. 1, 01.07.2007, p. 91-94.

Research output: Contribution to journalArticle

Chou, Sunwen ; Van Wechel, Laura C. ; Marousek, Gail I. / Cytomegalovirus UL97 kinase mutations that confer maribavir resistance. In: Journal of Infectious Diseases. 2007 ; Vol. 196, No. 1. pp. 91-94.
@article{b113af507ef94f59bf4ca27beb6a3516,
title = "Cytomegalovirus UL97 kinase mutations that confer maribavir resistance",
abstract = "The cytomegalovirus (CMV) UL97 kinase inhibitor maribavir (MBV) is undergoing clinical antiviral trials. Two clinical CMV isolates serially passaged in cell culture under MBV showed >20-fold increases in MBV resistance after the development of the UL97 mutation V353A in one of the isolates and of T409M in the other. Marker transfer studies confirmed that the V353A and T409M mutations conferred ∼15-fold and ∼80-fold increases, respectively, in MBV resistance without significantly affecting ganciclovir susceptibility. The 3 UL97 mutations now known to confer MBV resistance are located upstream of UL97 mutations linked to ganciclovir resistance, closer to kinase domains that are associated with adenosine triphosphate binding and phosphotransfer.",
author = "Sunwen Chou and {Van Wechel}, {Laura C.} and Marousek, {Gail I.}",
year = "2007",
month = "7",
day = "1",
doi = "10.1086/518514",
language = "English (US)",
volume = "196",
pages = "91--94",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "1",

}

TY - JOUR

T1 - Cytomegalovirus UL97 kinase mutations that confer maribavir resistance

AU - Chou, Sunwen

AU - Van Wechel, Laura C.

AU - Marousek, Gail I.

PY - 2007/7/1

Y1 - 2007/7/1

N2 - The cytomegalovirus (CMV) UL97 kinase inhibitor maribavir (MBV) is undergoing clinical antiviral trials. Two clinical CMV isolates serially passaged in cell culture under MBV showed >20-fold increases in MBV resistance after the development of the UL97 mutation V353A in one of the isolates and of T409M in the other. Marker transfer studies confirmed that the V353A and T409M mutations conferred ∼15-fold and ∼80-fold increases, respectively, in MBV resistance without significantly affecting ganciclovir susceptibility. The 3 UL97 mutations now known to confer MBV resistance are located upstream of UL97 mutations linked to ganciclovir resistance, closer to kinase domains that are associated with adenosine triphosphate binding and phosphotransfer.

AB - The cytomegalovirus (CMV) UL97 kinase inhibitor maribavir (MBV) is undergoing clinical antiviral trials. Two clinical CMV isolates serially passaged in cell culture under MBV showed >20-fold increases in MBV resistance after the development of the UL97 mutation V353A in one of the isolates and of T409M in the other. Marker transfer studies confirmed that the V353A and T409M mutations conferred ∼15-fold and ∼80-fold increases, respectively, in MBV resistance without significantly affecting ganciclovir susceptibility. The 3 UL97 mutations now known to confer MBV resistance are located upstream of UL97 mutations linked to ganciclovir resistance, closer to kinase domains that are associated with adenosine triphosphate binding and phosphotransfer.

UR - http://www.scopus.com/inward/record.url?scp=34250795232&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250795232&partnerID=8YFLogxK

U2 - 10.1086/518514

DO - 10.1086/518514

M3 - Article

C2 - 17538888

AN - SCOPUS:34250795232

VL - 196

SP - 91

EP - 94

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 1

ER -