Gerna Giuseppe, Percivalle Elena, Baldanti Fausto, Revello Maria Grazia
Servizio di Virologia, IRCCS Policlinico San Matteo, Pavia, Italy.
J Med Virol. 2002 Mar;66(3):335-9. doi: 10.1002/jmv.2150.
The development of a human cytomegalovirus (HCMV) vaccine for the prevention of perinatal disease is urgently needed. However, markers of HCMV attenuation are not defined at present. An in vitro model for the study of interactions of HCMV-infected human fibroblasts and peripheral blood polymorphonuclear leukocytes showed that (1) known laboratory-adapted HCMV strains as well as cell culture-adapted HCMV isolates were not transmitted to polymorphonuclear leukocytes; (2) each of the 80 HCMV recent isolates was consistently transmitted to polymorphonuclear leukocytes as both infectious virus and viral components (nucleic acid and proteins); and (3) all 15 polymorphonuclear leukocyte-tropic strains tested thus far were also endothelial cell-tropic. The in vitro transmissibility to polymorphonuclear leukocytes (and endothelial cells) is proposed as a surrogate marker of pathogenicity of HCMV strains. It seems reasonable to assume that a HCMV strain candidate for a vaccine be verified as deprived of the transfer property to polymorphonuclear leukocytes (and endothelial cells) before involvement in clinical trials assessing safety and immunogenicity.
迫切需要开发一种用于预防围产期疾病的人巨细胞病毒(HCMV)疫苗。然而,目前尚未确定HCMV减毒的标志物。一项关于HCMV感染的人成纤维细胞与外周血多形核白细胞相互作用的体外研究模型表明:(1)已知的实验室适应株以及细胞培养适应株的HCMV均不会传播至多形核白细胞;(2)80株近期的HCMV分离株中的每一株都能作为感染性病毒以及病毒成分(核酸和蛋白质)持续传播至多形核白细胞;(3)迄今为止测试的所有15株嗜多形核白细胞毒株也都是嗜内皮细胞的。体外对多形核白细胞(和内皮细胞)的传播性被提议作为HCMV毒株致病性的替代标志物。在参与评估安全性和免疫原性的临床试验之前,将候选HCMV毒株验证为缺乏向多形核白细胞(和内皮细胞)的转移特性似乎是合理的。