Novel mutation in the CMV UL97 gene associated with resistance to ganciclovir therapy

被引:31
作者
Mendez, JC
Sia, IG
Tau, KR
Espy, MJ
Smith, TF
Chou, S
Paya, CV
机构
[1] Mayo Clin, Div Infect Dis, Rochester, MN 55905 USA
[2] Dept Vet Affairs, Med Ctr, Portland Div, Portland, OR USA
关键词
D O I
10.1097/00007890-199903150-00020
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Cytomegalovirus (CMV) strains resistant to ganciclovir have been associated with specific mutations in the UL97 and UL54 genes. The UL97 gene of a CMV strain isolated from a renal transplant recipient before and after 438 days of ganciclovir treatment was amplified by polymerase chain reaction and sequenced. A novel mutation resulting in deletion of codons 595 to 603 was identified in the viral DNA from specimens obtained after, but not before, prolonged ganciclovir therapy. Clinical and virological resolution of CMV disease occurred after switching to foscarnet therapy. Although many ganciclovir resistance mutations have been mapped to the UL97 codon range 591-607, this one is unusual in that it involves deletion of half these codons. Because UL97 seems to be necessary for effective CMV replication, this deletion suggests that much of codons 591-607 can be removed without destroying the biological function of UL97, and that this codon range can be altered in various ways to affect ganciclovir susceptibility. Rapid, flexible genotypic assays directed at this part of UL97 may facilitate the early recognition of ganciclovir resistance.
引用
收藏
页码:755 / 757
页数:3
相关论文
共 13 条
[1]  
Baldanti F, 1998, ANTIMICROB AGENTS CH, V42, P444
[2]   ALPHA-HERPESVIRUSES, BETA-HERPESVIRUSES AND GAMMA-HERPESVIRUSES ENCODE A PUTATIVE PHOSPHOTRANSFERASE [J].
CHEE, MS ;
LAWRENCE, GL ;
BARRELL, BG .
JOURNAL OF GENERAL VIROLOGY, 1989, 70 :1151-1160
[3]   FREQUENCY OF UL97 PHOSPHOTRANSFERASE MUTATIONS RELATED TO GANCICLOVIR RESISTANCE IN CLINICAL CYTOMEGALOVIRUS ISOLATES [J].
CHOU, SW ;
GUENTZEL, S ;
MICHELS, KR ;
MINER, RC ;
DREW, WL .
JOURNAL OF INFECTIOUS DISEASES, 1995, 172 (01) :239-242
[4]   Evolution of mutations conferring multidrug resistance during prophylaxis and therapy for cytomegalovirus disease [J].
Chou, SW ;
Marousek, G ;
Guentzel, S ;
Follansbee, SE ;
Poscher, ME ;
Lalezari, JP ;
Miner, RC ;
Drew, WL .
JOURNAL OF INFECTIOUS DISEASES, 1997, 176 (03) :786-789
[5]   ANALYSIS OF THE UL97 PHOSPHOTRANSFERASE CODING SEQUENCE IN CLINICAL CYTOMEGALOVIRUS ISOLATES AND IDENTIFICATION OF MUTATIONS CONFERRING GANCICLOVIR RESISTANCE [J].
CHOU, SW ;
ERICE, A ;
JORDAN, MC ;
VERCELLOTTI, GM ;
MICHELS, KR ;
TALARICO, CL ;
STANAT, SC ;
BIRON, KK .
JOURNAL OF INFECTIOUS DISEASES, 1995, 171 (03) :576-583
[6]   PREVALENCE OF RESISTANCE IN PATIENTS RECEIVING GANCICLOVIR FOR SERIOUS CYTOMEGALOVIRUS-INFECTION [J].
DREW, WL ;
MINER, RC ;
BUSCH, DF ;
FOLLANSBEE, SE ;
GULLETT, J ;
MEHALKO, SG ;
GORDON, SM ;
OWEN, WF ;
MATTHEWS, TR ;
BUHLES, WC ;
DEARMOND, B .
JOURNAL OF INFECTIOUS DISEASES, 1991, 163 (04) :716-719
[7]   PROGRESSIVE DISEASE DUE TO GANCICLOVIR-RESISTANT CYTOMEGALO-VIRUS IN IMMUNOCOMPROMISED PATIENTS [J].
ERICE, A ;
CHOU, S ;
BIRON, KK ;
STANAT, SC ;
BALFOUR, HH ;
JORDAN, MC .
NEW ENGLAND JOURNAL OF MEDICINE, 1989, 320 (05) :289-293
[8]   COMPARISON OF 3 METHODS FOR EXTRACTION OF VIRAL NUCLEIC-ACIDS FROM BLOOD CULTURES [J].
ESPY, MJ ;
PATEL, R ;
PAYA, CV ;
SMITH, TF .
JOURNAL OF CLINICAL MICROBIOLOGY, 1995, 33 (01) :41-44
[9]   The UL97 gene product of human cytomegalovirus is an early-late protein with a nuclear localization but is not a nucleoside kinase [J].
Michel, D ;
Pavic, I ;
Zimmermann, A ;
Haupt, E ;
Wunderlich, K ;
Heuschmid, M ;
Mertens, T .
JOURNAL OF VIROLOGY, 1996, 70 (09) :6340-6346
[10]   Cytomegalovirus prophylaxis in solid organ transplant recipients [J].
Patel, R ;
Snydman, DR ;
Rubin, RH ;
Ho, M ;
Pescovitz, M ;
Martin, M ;
Paya, CV .
TRANSPLANTATION, 1996, 61 (09) :1279-1289