Enhancement of natural killer cell cytotoxicity by the human herpesvirus-7 via IL-15 induction

Abstract

NK cells, a key component of the innate immune system, are known to play an important role against viral infections. Previously, we reported that the human herpesvirus-6 (HHV-6) induces IL-15 in human PBMC and increases their NK activity. We describe in this work that another human herpesvirus, HHV-7, which shares genomic homology with HHV-6, also causes up-regulation of NK cell cytotoxicity via IL-15 induction. The NK cell activity of the PBMC from different donors displayed a variable range of enhancement after treatment with HHV-7. This enhancement occurred within a few hours of exposure to the virus and was blocked by Abs to IL-15, but not to other cytotoxicity-enhancing cytokines (i.e., to IFN-gamma, IL-2, TNF-alpha, or IL-12). Our results also show that this HHV-7-induced IL-15-mediated activation of NK cells occurs via IL-2R, since HHV-7-enhanced NK cytotoxic activity could be blocked completely by anti-IL-2R beta-chain mAb (anti-CD122). The up-regulation of NK cell cytotoxicity did not require infectious virus, as the use of UV-irradiated HHV-7 produced similar results. This effect was virus specific because it was abrogated by neutralizing the virus with human sera containing Abs to HHV-7. We also found increased amount of IL-15 transcripts in HHV-7-treated PBMC as compared with the untreated PBMC. Taken together, these results would suggest that host responds to HHV-7 infection by up-regulating IL-15 production, which then results in an enhancement of NK cell activity; this, in turn, may play a major role in the control of the viral infection.