Human cytomegalovirus. Stimulation of [3H] release from [3H]-arachidonic acid prelabelled cells

Abstract

Exposure of human lung fibroblasts to human cytomegalovirus (HCMV) stimulated a rapid increase in the release of [3H] from cells prelabelled with radiolabelled arachidonic acid ([3H]AA). Maximum stimulation of [3H] release was observed at 20 min postinfection and was quantitatively similar to that induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA: 10 nM) or fetal calf serum (5%). The level of [3H] release was dependent on the multiplicity of infection, and appeared to be mediated by a component(s) of the virion, since the findings from three series of experiments suggested that neither infectious virus, nor HCMV-specific macromolecular synthesis was required for stimulation of [3H] release. (1) Inactivation of HCMV infectivity with ultra-violet (UV) light (approximately 254 nm, 4.80 x 10(4) ergs/mm2) did not diminish the stimulation of [3H] release. (2) Significant reduction in the level of [3H] release was not observed when infected cells were maintained in the presence of a protein synthesis inhibitor, cycloheximide (50 micrograms/ml), or an inhibitor of mRNA synthesis, 3'-deoxyadenosine (cordycepin, 50 micrograms/ml). (3) No correlation was established between the expression of HCMV immediate early (IE) antigens and the induction of [3H] release, since there was little, if any, synthesis of HCMV IE antigen detectable by anticomplement immunofluorescence through the first 30 min postinfection. These findings suggesting that the HCMV particle rapidly stimulates AA metabolism are consistent with the view that the interaction of a HCMV virion component(s) with the cell surface may initiate membrane-associated events similar to those induced by growth factors.