Role of IL-15 on monocytic resistance to human herpesvirus 6 infection

Interleukin-15 (IL-15) is a cytokine that possesses a variety of biological functions, including stimulation and maintenance of cellular immune responses. Recently, it has been demonstrated that Human Herpes virus type 6 (HHV-6) enhances NK activity of human PBMC by inducing IL-15. HHV-6 is a typical immunosuppressive agent, as suggested by its tropism for both CD4+ and CD8+ T cells, B cells, monocytes/macrophages, megakaryocytes and NK cells. Moreover, several studies have indicated that mononuclear phagocyte resistance to virus infection is influenced by the cellular differentiation state. This paper describes the effect of pretreatment "in vitro" with IL-15 on the resistance of human monocytes (HM) to HHV-6 infection. Our results demonstrate that undifferentiated HM were highly resistant to HHV-6 infection, whereas HM pretreated with human recombinant IL-15 showed an increased permissiveness for HHV-6 infection. This permissiveness was characterised by higher release of extracellular virus as well as an increased percentage of antigen positive cells. Moreover, we evaluated IL-15 production after the addition of HHV-6 to monocytes precultured in different experimental conditions. Our data indicate that HHV-6-induced IL-15 production by human monocytes is not affected by the condition of "in vitro" precultivation/differentiation. Furthermore, the neutralization of IL-15 induced by HHV-6 in differentiated monocytes did not affect viral replication. These findings suggest that IL-15 acts only on the mechanisms of cellular differentiation, rendering HM more susceptible to HHV-6 infection, without interfering with virus replication.