Insoluble substances produced from human cytomegalovirus-infected cells induce deaths of nearby cells through non-classical death signal pathway (P6116)

Abstract

Abstract Human cytomegalovirus (HCMV) has many strategies to evade the host immune system, and eventually resides in some cells in latency. Although the involvement of Fas ligand in T cell death was reported in the pathogenesis of retinitis with HCMV infection to retinal pigment epithelial cells, the cell death near other lesions caused by HCMV infection was not studied in detail by now. The insoluble substances derived from HCMV-infected fibroblasts, induce the deaths of variety of cell lines including Jurkat, HL-60, K562, U937 and THP-1 cells, but not of fibroblasts, HEK293 and U373MG. They were resistant to treatment with 56°C for 30 min to lose death induceability to Jurkat cells. Cell death of Jurkat cells by these substances were not inhibited by the simultaneous treatment with neutralizing antibodies to Fas ligand or TRAIL, or caspase inhibitors. Insoluble substances induced cleavages of poly ADP-ribose polymerase-1 into 89 kDa fragment, but not through caspase 3, 7 or 9 pathway in Jurkat cells. AIF was detected in the cytoplasmic fraction, but not in the nuclear fraction of Jurkat cells from 6 hours following exposure to them. This result suggested AIF was not translocated from mitochondria to nucleus in Jurkat cells by the stimulation with insoluble substances. Collectively human cytomegalovirus infection would induce the death of myeloid and lymphoid cells near the infection site through non-classical death signal pathway.