Background:  Natural killer (NK) cells are critical in the innate immune response to infection by lysing infected cells and secreting cytokines and chemokines without prior sensitisation. In HIV-1 infection the number and cytolytic function of NK cells is reduced. Furthermore, lymphocytes of HIV-1 patients show increased expression of membrane-bound Fas and higher sensibility to Fas-mediated apoptosis which is one of the mechanisms responsible for decreased CD4 T cells. Co-infections can affect the course of HIV infection. Persistent co-infection with the apathogenic human RNA virus GBV-C leads to prolonged AIDS-free survival and higher CD4⁺ cell counts compared with GBV-C^­ HIV-1 patients.

Methods:  Peripheral blood mononucleara cells (PBMC) from patients and healthy volunteers were analyzed by gating on CD3^­/CD56⁺ NK cells using multicolour flow cytometry. For cytokine production PBMC were fixed, permeabilized, and stained for intracellular cytokines.

Results:  Analysis of NK cells revealed identical phenotypes with respect to NK subpopulations (CD56^dim/bright, CD16), NK receptors (NKp30, NKp46), intracellular cytokine (e.g., TNF-a/IFN-g), and perforin content as well as the GBV-C receptor CD81 and the HIV-1 co-receptors CXCR4 and CCR5 in untreated HIV-1-infected patients with and without GBV-C co-infection. GBV-C co-infected patients showed a slight increase in NK cells expressing activation markers (CD69, CD25, NKp44). Furthermore, NK cells of untreated GBV-C/HIV-1-co-infected patients displayed a significant reduction of Fas (CD95) expression. This effect was abrogated by ART, as NK cells of HIV-1-infected patients receiving HAART had comparable Fas expression in GBV-C co-infected and non-co-infected individuals.

Conclusions:  GBV-C leads to decreased Fas expression on NK cells. This effect might contribute to the beneficial course of HIV-1 patients with GBV-C co-infection.