Inhibition of ERK and proliferation in NK cell lines by soluble HLA-Ereleased from Japanese encephalitis virus infected cells

tProductive infection of human endothelial cells with Japanese encephalitis virus (JEV), a single strandedRNA virus induces shedding of sHLA-E. We show here that sHLA-E that is released upon infection with thisflavivirus can inhibit IL-2 and PMA mediated ERK 1/2 phosphorylation in two NK cell lines, Nishi and NKL.Virus infected or IFN- treated cell culture supernatants containing sHLA-E were found to partially inhibitIL-2 mediated induction of CD25 molecules on NKL cells. It was also found that sHLA-E could inhibit IL-2induced [3H]-thymidine incorporation suggesting that, similar to cell surface expressed HLA-E, sHLA-Ecould also inhibit NK cell responses. Hence JEV-induced shedding of sHLA-E needs further investigationto better understand immune responses in JEV infections since it may have a role in viral evasion of NKcell responses.