EPSTEIN-BARR-VIRUS INFECTS AND INDUCES APOPTOSIS IN HUMAN NEUTROPHILS

The role of neutrophils during Epstein-Barr virus (EBV) infection is n ot known. Disruption of the initial and nonspecific immune response ma y favor the spread of EBV infection. We have previously shown that EBV interacts with human neutrophils and modulates protein expression. In this study we have investigated the ability of EBV to infect neutroph ils. Electron microscopy studies showed penetration of virus and its s ubsequent localization to the nucleus. The presence of viral genomes i n isolated nuclei from neutrophils was also shown by polymerase chain reaction (PCR). Expression of viral transcripts like EBNA-2 (Epstein-B arr nuclear antigen-2) and ZEBRA (BamHI Z EBV replication activator) w as not detected by reverse transcriptase (RT)PCR, suggesting that EBV does not seem to establish a latent or a lytic infection in neutrophil s. However, at 20 hours post-EBV infection, 77% of cells were apoptoti c as compared to 22% in uninfected cell cultures, as evaluated by flow cytometry, This EBV-induced apoptosis was prevented by the addition o f granulocyte-macrophage colony-stimulating factor to the cell culture s, Apoptotic cell death seems to implicate the Fas/Fas ligand (L) path way, as reflected by an increase of Fas/Fas L expression on neutrophil s treated with EBV and an increase of soluble Fas L, which may functio n in an autocrine/paracrine pathway to mediate cell death. Lastly, EBV genome was detected from neutrophils of infectious mononucleosis (IM) patients in contrast to neutrophils obtained from healthy EBV-seropos itive donors. Our findings on the interactions of EBV with neutrophils will then provide new insights on the immunosuppressive effects assoc iated with EBV infection. (C) 1998 by The American Society of Hematolo gy.