Horizontal transfer of DNA by the uptake of apoptotic bodies.
In this study we have raised the question of whether DNA can be transferred from one cell to another by phagocytosis of apoptotic bodies. We have used integrated copies of the Epstein-Barr virus (EBV) as a marker to follow the fate and expression pattern of apoptotic DNA in the phagocytotic host. Apoptosis was induced in EBV-carrying cell lines by irradiation before cultivation with either human fibroblasts, macrophages, or bovine aortic endothelial cells. Analysis of the expression pattern of EBV-encoded genes was performed by immunofluorescent staining as well as in situ hybridization. Cocultivation of apoptotic bodies from lymphoid cell lines containing integrated but not episomal copies of EBV resulted in expression of the EBV-encoded genes EBER and EBNA1 in the recipient cells at a high frequency. Fluorescence in situ hybridization analysis showed uptake of human chromatin as well as integrated EBV-DNA into the nuclei of bovine aortic endothelial cells. These data show that DNA may be rescued and reused from apoptotic bodies by somatic cells. In addition, our findings suggest that apoptotic bodies derived from EBV-carrying B lymphocytes may serve as the source of viral transfer to cells that lack receptors for the EBV virus in vivo.
Holmgren
L
L
Center for Genomic Research and Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden. Lars.Holmgren@mtc.ki.se
Szeles
A
A
Rajnavölgyi
E
E
Folkman
J
J
Klein
G
G
Ernberg
I
I
Falk
K I
KI
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002417:Cattle; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics*; D004730:Endothelium, Vascular / Q000473:pathology / Q000821:virology; D005347:Fibroblasts / Q000473:pathology / Q000821:virology; D022761:Gene Transfer, Horizontal; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D008264:Macrophages / Q000473:pathology / Q000821:virology; D010587:Phagocytosis
D004279:DNA, Viral