Snoeck R, Schols D, Sadzot-Delvaux C, Cloes J M, Andrei G, De Clercq E, Piette J, Rentier B
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
J Virol Methods. 1992 Aug;38(2):243-54. doi: 10.1016/0166-0934(92)90114-s.
Varicella zoster virus (VZV) is responsible for a primary infection (varicella) and, upon reactivation, zoster, which in immunocompromised patients, may both lead to life-threatening disseminated disease. There is a great need for antiviral compounds that are effective inhibitors of VZV replication and for rapid and accurate methods for evaluating viral sensitivity to candidate anti-VZV drugs. With the monoclonal antibody (mAb) (VL8), which is directed against the gpI of VZV, and using the fluorescence-activated cell sorter (FACS) we could readily demonstrate expression of the VZV gpI antigen at 3-4 days after VZV infection. (E)-5-(2-Bromovinyl)-2'-deoxyuridine (BVDU), (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA) and (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMC) were shown to be potent inhibitors of VZV replication by this assay. HPMPA and HPMPC were also active against thymidine kinase-deficient (TK-) VZV whereas BVDU was not. The flow cytometric method based on the use of mAb VL8 may be of considerable help for the early diagnosis of VZV infection and evaluation of viral sensitivity to antiviral drugs.
水痘带状疱疹病毒(VZV)可引发原发性感染(水痘),病毒再激活时则导致带状疱疹,在免疫功能低下的患者中,这两种情况都可能引发危及生命的播散性疾病。目前迫切需要有效的VZV复制抑制剂类抗病毒化合物,以及用于评估病毒对候选抗VZV药物敏感性的快速准确方法。利用针对VZV糖蛋白I(gpI)的单克隆抗体(mAb)(VL8),并借助荧光激活细胞分选仪(FACS),我们能够轻易地证明在VZV感染后3 - 4天VZV gpI抗原的表达。通过该检测方法,(E)-5-(2-溴乙烯基)-2'-脱氧尿苷(BVDU)、(S)-9-(3-羟基-2-膦酰甲氧基丙基)腺嘌呤(HPMPA)和(S)-1-(3-羟基-2-膦酰甲氧基丙基)胞嘧啶(HPMC)被证明是VZV复制的有效抑制剂。HPMPA和HPMPC对胸苷激酶缺陷型(TK-)VZV也有活性,而BVDU则没有。基于mAb VL8的流式细胞术方法可能对VZV感染的早期诊断以及评估病毒对抗病毒药物的敏感性有很大帮助。