Background Lymphocyte antigen 6 complex locus E (LY6E) is a type I interferon-inducible gene and has been shown to enhance viral replication (Nature 2011, 472:481). However, the underlying mechanism and its role in HIV-1 infection remains to be determined.
Methods LY6E expression was quantified in HIV-infected subjects and HIV-seronegative individuals, its associations with CD4+ T cell counts and viral loads in HIV-infected subjects were determined. In addition, the roles of LY6E in regulating innate immune responses in HIV-1 infection were further investigated in vitro in monocytes.
Results LY6E was significantly up-regulated in HIV-infected subjects, its expression was reversely correlated with CD4+ T cell counts and positively with the viral loads. LY6E is mainly expressed on monocytes through it is detectable in different subpopulations in peripheral blood mononuclear cells. The infection of Monocyte by HIV-1 in vitro resulted in the up-regulation of LY6E, knocking down LY6E expression by siRNA profoundly enhanced the production of proinflammatory cytokines and Type 1 interferon, in contrast, over-expression of LY6E led to the suppression of CD14 expression and resulted in the reduction of both proinflammatory cytokines and Type I interferons. Over-expression of CD14 could overcome the LY6E-mediated suppression.
Conclusion For the first time we identified that LY6E is an inhibitory molecule on monocytes and is correlated to HIV disease progression, the down-regulation of innate immunity by LY6E was accomplished by reducing CD14.