Snoeck R, Gérard M, Sadzot-Delvaux C, Andrei G, Balzarini J, Reymen D, Ahadi N, De Bruyn J M, Piette J, Rentier B
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
J Med Virol. 1994 Apr;42(4):338-47. doi: 10.1002/jmv.1890420404.
Varicella zoster virus (VZV) is recognized as one of the major viral pathogens reactivated in patients with the acquired immune deficiency syndrome (AIDS). We report the case of meningoradiculoneuritis in an AIDS patient,associated with the isolation in the cerebrospinal fluid (CSF) of a thymidine kinase (TK)-deficient, acyclovir (ACV)-resistant strain of VZV. Although the virus was sensitive in vitro to phosphonoformate (PFA), the patient did not improve during PFA therapy and finally died. Several VZV strains isolated from this patient (including two isolates from the patient's CSF) were analyzed for their TK activity and subsequently the viral TK gene was sequenced showing a major deletion leading to a truncated protein. Their susceptibility to several antiviral agents including ACV, PFA, (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), 9-beta-D-arabinofuranosyladenine (vidarabine), (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (HPMPC), and (S)-9-(3-hydroxy-2-phosphonyl-methoxypropyl)adenine (HPMPA) was evaluated. All the virus strains isolated from this patient remained sensitive to HPMPA and HPMPC, pointing to the potential usefulness of these acyclic nucleoside phosphonates for the treatment of ACV-resistant VZV infections in immunocompromised patients.
水痘带状疱疹病毒(VZV)被认为是在获得性免疫缺陷综合征(AIDS)患者中重新激活的主要病毒病原体之一。我们报告了一例AIDS患者发生的脑脊膜神经根神经炎病例,该病例与在脑脊液(CSF)中分离出一株胸苷激酶(TK)缺陷、对阿昔洛韦(ACV)耐药的VZV毒株有关。尽管该病毒在体外对膦甲酸(PFA)敏感,但患者在PFA治疗期间并未好转,最终死亡。对从该患者分离出的几种VZV毒株(包括从患者脑脊液中分离出的两株)进行了TK活性分析,随后对病毒TK基因进行测序,结果显示存在一个主要缺失,导致产生截短蛋白。评估了它们对几种抗病毒药物的敏感性,包括ACV、PFA、(E)-5-(2-溴乙烯基)-2'-脱氧尿苷(BVDU)、9-β-D-阿拉伯呋喃糖基腺嘌呤(阿糖腺苷)、(S)-1-(3-羟基-2-膦酰甲氧基丙基)胞嘧啶(HPMPC)和(S)-9-(3-羟基-2-膦酰甲氧基丙基)腺嘌呤(HPMPA)。从该患者分离出的所有病毒毒株对HPMPA和HPMPC仍敏感,这表明这些无环核苷膦酸盐在治疗免疫功能低下患者的ACV耐药VZV感染方面具有潜在用途。