Lack of transmission to polymorphonuclear leukocytes and human umbilical vein endothelial cells as a marker of attenuation of human cytomegalovirus.

Abstract

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.