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 respon ses. 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 typica l 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 resis tance to virus infection is influenced by the cellular differentiation stat e. 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 dem onstrate that undifferentiated HM were highly resistant to HHV-6 infection, whereas HM pretreated with human recombinant IL-15 showed an increased per missiveness for HHV-6 infection. This permissiveness was characterised by h igher release of extracellular virus as well as an increased percentage of antigen positive cells. Moreover, we evaluated IL-15 production after the a ddition of HHV-6 to monocytes precultured in different experimental conditi ons. Our data indicate that HHV-6-induced IL-15 production by human monocyt es is not affected by the condition of "in vitro" precultivation/differenti ation. Furthermore, the neutralization of IL-15 induced by HHV-6 in differe ntiated monocytes did not affect viral replication. These findings suggest that IL-15 acts only on the mechanisms of cellular differentiation, renderi ng HM more susceptible to HHV-6 infection, without interfering with virus r eplication.