TY - JOUR
T1 - Viral DNA polymerase mutations associated with drug resistance in human cytomegalovirus
AU - Chou, Sunwen
AU - Lurain, Nell S.
AU - Thompson, Kenneth D.
AU - Miner, Richard C.
AU - Drew, W. Lawrence
N1 - Funding Information:
Received 8 November 2002; accepted 31 January 2003; electronically published 16 June 2003. Financial support: Department of Veterans Affairs research funds; National Institutes of Health (grant AI-39938); American Lung Association of Metropolitan Chicago. Reprints or correspondence: Dr. Sunwen Chou, VA Medical Center P3ID, 3710 Southwest US Veterans Hospital Rd., Portland, OR 97201 (chous@ohsu.edu).
PY - 2003/7/1
Y1 - 2003/7/1
N2 - Certain mutations in the viral DNA polymerase (pol) gene are known to confer drug resistance when transferred to susceptible human cytomegalovirus (CMV) strains, whereas other putative resistance mutations remain unproven. A new marker-transfer technique was used to produce recombinant CMV strains, to determine the drug susceptibility phenotypes conferred by 10 pol mutations (9 observed in clinical isolates). Various degrees of resistance to ganciclovir and cidofovir were conferred by mutations D301N, N410K, D413E, T503I, and L516R, which are located within exonuclease functional domains where D301N and D413E affect highly conserved residues. Mutations A692S, E756K, and E756D, which are not located within recognized functional domains, each conferred foscarnet resistance. This study significantly increases the number of confirmed CMV pol resistance mutations, at both conserved and nonconserved loci, with implications for molecular mechanisms and the genotypic diagnosis of antiviral resistance.
AB - Certain mutations in the viral DNA polymerase (pol) gene are known to confer drug resistance when transferred to susceptible human cytomegalovirus (CMV) strains, whereas other putative resistance mutations remain unproven. A new marker-transfer technique was used to produce recombinant CMV strains, to determine the drug susceptibility phenotypes conferred by 10 pol mutations (9 observed in clinical isolates). Various degrees of resistance to ganciclovir and cidofovir were conferred by mutations D301N, N410K, D413E, T503I, and L516R, which are located within exonuclease functional domains where D301N and D413E affect highly conserved residues. Mutations A692S, E756K, and E756D, which are not located within recognized functional domains, each conferred foscarnet resistance. This study significantly increases the number of confirmed CMV pol resistance mutations, at both conserved and nonconserved loci, with implications for molecular mechanisms and the genotypic diagnosis of antiviral resistance.
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U2 - 10.1086/375743
DO - 10.1086/375743
M3 - Article
C2 - 12825168
AN - SCOPUS:0038574429
SN - 0022-1899
VL - 188
SP - 32
EP - 39
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 1
ER -