Human herpesvirus-6 enhances natural killer cell cytotoxicity via IL-15.
The marked tropism of human herpesvirus-6 (HHV-6) for natural killer (NK) cells and T lymphocytes has led us to investigate the effect of HHV-6 on cellular cytotoxicity. We describe here how HHV-6 infection of peripheral blood mononuclear cells (PBMC) leads to upregulation of their NK cell cytotoxicity. The induction of NK cell activity by HHV-6 was abrogated by monoclonal antibodies (mAbs) to IL-15 but not by mAbs to other cytokines (IFN-alpha, IFN-gamma, TNF-alpha, TNF-beta, IL-2, IL-12) suggesting that IL-15 secreted in response to viral infection was responsible for the observed effect. Furthermore, NK activation by HHV-6 was blocked with mAb to CD122, as well as by human anti-HHV-6 neutralizing antibodies. Using RT-PCR, we were able to detect IL-15 mRNA upregulation in purified monocyte and NK cell preparations. IL-15 protein synthesis was increased in response to HHV-6. Finally, addition of IL-15 to PBMC cultures was found to severely curtail HHV-6 expression. Taken together, our data suggest that enhanced NK activity in response to viral infection represent a natural anti-viral defense mechanism aimed at rapidly eliminating virus-infected cells.
Flamand
L
L
Pediatric Research Center, University of Montreal, Quebec, Canada.
Stefanescu
I
I
Menezes
J
J
D001483:Base Sequence; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006566:Herpesviridae Infections / Q000276:immunology* / Q000378:metabolism; D015654:Herpesvirus 6, Human; D006801:Humans; D019409:Interleukin-15; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D015854:Up-Regulation
D019409:Interleukin-15; D007378:Interleukins; D012333:RNA, Messenger