In vitro selection of human cytomegalovirus variants unable to transfer virus and virus products from infected cells to polymorphonuclear leukocytes and to grow in endothelial cells

Four human cytomegalovirus (HCMV) isolates from different clinical sources were extensively propagated in human embryonic lung fibroblasts (HELF), Pla que isolates from each of the four virus strains were evaluated for their a bility to be transferred to polymorphonuclear leukocytes (PMNL) and to grow in endothelial cells (EC), While all four of the clinical strains were fou nd to be both PMNL- and PC-tropic, variants were identified from each of th e four strains that lacked both biological properties, while three of the f our parental strains lost their transfer capacity before passage 50 in HELF . It was demonstrated that one of the four field isolates (VR6110) and its transfer-deficient variant were genetically related, but showed different c urves of virus yield in HELF, In addition, neither the immediate-early (IE) mRNA nor the IE protein p72 were found to be transferred to PMNL before 72 h post-infection (late in infection) or in the presence of viral DNA repli cation inhibitors. These findings link EC and PMNL tropism and suggest that PMNL tropism is a late HCMV function.