INFECTION OF NATURAL-KILLER-CELLS BY HUMAN HERPESVIRUS-6

NATURAL killer (NK) cells are a functionally defined subset of non-T, non-B lymphocytes of bone marrow origin, which induce lysis of selected target cells, including neoplastic and virus-infected cells1-3. The NK cell function provides an important mechanism of primary defence against viruses in vivo, as demonstrated by the occurrence of multiple herpesvirus infections in patients congenitally lacking NK cells4,5. Here we show that functionally competent CD3- NK clones can be productively infected by human herpesvirus 6 (HHV-6)6, a T-lymphotropic DNA virus7 that may play a role in the acquired immunodeficiency syndrome (AIDS)8 and in the chronic fatigue syndrome9, two disorders associated with a defective NK cell activity10-15. The infection is cytopathic and induces de novo expression of CD4, an antigen not expressed within the NK lineage16,17, thereby predisposing NK cells to infection by human immunodeficiency virus type 1 (HIV-1). These results provide evidence that a herpesvirus can directly target and kill NK cells, a potential strategy to suppress the natural anti-viral immunity of the host.