CONICET | Buscador de Institutos y Recursos Humanos

Background: Natural Killer cells (NK) play an important role in combating viral infections. Several studies report phenotypical NK alterations during human chronic viral infections but few studies have been done in acute viral infections and there are no reports in relation with Hantavirus Pulmonary Syndrome (HPS). Therefore we studied circulating NK from HPS patients infected with Andes virus (ANDV) to seek for alterations that may be functionally relevant.Methods: ANDV+ patients (n=17), healthy subjects (HS, n=13) and seronegative patients with acute respiratory symptoms (ARS, n=14) were enrolled. Their stabilized blood samples (TransfixTM) were stained and analyzed by flow cytometry. In vitro assays were performed to evaluate down-regulation of CD16 expression in normal NK, by exposing them to ANDV+ patient sera (n=15) in complex with viral antigens (i.e: immune complexes).Results: Interestingly, among NK subsets of ANDV+ patients we saw decreased CD56dim/CD16hi and increased CD56negNK with respect to HS (p 0.001) and ARS (p 0.005). Additionally, there was a significant increase with respect to HS in a subset defined as CD56dimCD16low/neg (p 0.001). Moreover, we were able to reproduce this drop of CD16 expression on CD56dim subset through in vitro assays by culturing normal NK during 24hs with immune complexes (p 0.05).Conclusions: ANDV+ patients have altered proportions of functional peripheral blood NK cell subsets as well as increased levels of known as dysfunctional NK cells, usually present in chronic viral infections like AIDS or HCV. In addition, our results suggest that CD56dimCD16low/neg could originate from endogenous activation of the Antibody Dependent Cellular Cytotoxicity mechanism.