Chou S, Marousek G, Guentzel S, Follansbee S E, Poscher M E, Lalezari J P, Miner R C, Drew W L
Medical and Research Services, VA Medical Center, Oregon Health Sciences University, Portland 97201, USA.
J Infect Dis. 1997 Sep;176(3):786-9. doi: 10.1086/517302.
In a human immunodeficiency virus-infected subject, cytomegalovirus (CMV) isolated 9 months after the patient began oral ganciclovir prophylaxis was resistant to ganciclovir and cidofovir and contained mutations in both UL97 and Pol coding regions. At 1 year, retinitis developed, which progressed despite intravenous ganciclovir followed by foscarnet and then cidofovir. A subsequent buffy coat virus isolate was resistant to all three drugs and contained new mutations in UL97 and Pol. By individually transferring the observed mutations to laboratory strain AD169, it was shown that a mutation at codon 603 of UL97 conferred resistance to ganciclovir, a mutation at codon 412 of Pol conferred resistance to both ganciclovir and cidofovir, and a mutation at codon 802 of Pol conferred resistance to ganciclovir and foscarnet. This case illustrates the development of multidrug resistance during prolonged exposure to antiviral therapy for CMV and cross-resistance arising from point mutations in the CMV Pol gene.
在一名人类免疫缺陷病毒感染患者中，患者开始口服更昔洛韦预防治疗9个月后分离出的巨细胞病毒（CMV）对更昔洛韦和西多福韦耐药，且UL97和Pol编码区均有突变。1年后，患者发生视网膜炎，尽管先后静脉注射更昔洛韦、膦甲酸钠，然后使用西多福韦治疗，病情仍进展。随后从血沉棕黄层分离出的病毒对这三种药物均耐药，且UL97和Pol出现新的突变。通过将观察到的突变分别转移至实验室菌株AD169，结果显示UL97第603位密码子的突变赋予了对更昔洛韦的耐药性，Pol第412位密码子的突变赋予了对更昔洛韦和西多福韦的耐药性，Pol第802位密码子的突变赋予了对更昔洛韦和膦甲酸钠的耐药性。该病例说明了长期接受CMV抗病毒治疗期间多药耐药性的产生以及CMV Pol基因点突变引起的交叉耐药性。
