ANALYSIS OF THE INTERACTION OF MATURING NK CELLS WITHREPLICATING VIRUSES: STRONG UPREGULATION OF NCREXPRESSION AND OF CYTOTOXICITY BY HSV-1, NOT BY HIV-1

Compromised control of microorganism or tumor spreading are associated in some instances to alterations of NK cell function. Mechanisms underlying this dysfunction are still unclear and may involve perturbations of NK cell differentiation in the presence of pathogen replication. We studied an ‘‘in vitro’’ model of NK cell differentiation from highly immature CD341Lin- precursors in the presence of replicating HIV-1 and HSV-1. No significant downregulation in NCR molecule expression and no impairment in the cytolytic capability of NK precursors were evident with HIV-1. On the contrary, the presence of productively HSV-1-infected cells induced an increased surface NCR molecule density resulting in significantly increased cytolytic activity. Importantly the HSV-mediated effect, is limited to maturing NK cells, and does not involve peripheral blood mature NK. Analysis of TLR expression on NK cells revealed augmented expression of the intracellular TLR9 molecule in CD561CD332 NK cell precursors in the presence of replicating HSV-1, but not of HIV-1. Thus, virus replication at sites of NK cell precursor development (e.g.: lymph node, bone marrow) may have different outcomes depending on the interaction between invading viruses and maturing NK cells and may contribute to success or failure to control virus replication/spread.