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Human X‐ DING ‐ CD 4 mediates resistance to HIV ‐1 infection through novel paracrine‐like signaling
Author(s) -
Sachdeva Rakhee,
Li Yuchang,
Shilpi Rasheda Y.,
Simm Malgorzata
Publication year - 2015
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13192
Subject(s) - paracrine signalling , transcription factor , biology , microbiology and biotechnology , interferon , innate immune system , immune system , immunology , receptor , gene , biochemistry
X‐ DING ‐ CD 4 is a novel phosphatase mediating antiviral responses to HIV ‐1 infection. This protein is constitutively expressed and secreted by HIV ‐1 resistant CD 4 + T cells and its m RNA transcription is up‐regulated in peripheral blood mononuclear cells from HIV ‐1 elite controllers. The secreted/soluble X‐ DING ‐ CD 4 protein form is of particular importance because it blocks virus transcription when added to HIV ‐1 susceptible cells. The present study aimed to determine the contribution of this factor to the induction of the antiviral response in target cells. We found that soluble X‐ DING ‐ CD 4 enters cells by endocytosis and that influx of this protein induced transcription of interferon‐α and endogenous X‐ DING ‐ CD 4 m RNA in transformed CD 4 + T cells and primary macrophages. Treatment of HIV ‐1 susceptible cells with exogenous X ‐ DING ‐ CD 4 caused depletion of phosphorylated p50 and p65 nuclear factor kappa β subunits and a significant reduction in p50/p65 nuclear factor kappa β binding to the HIV ‐1 long terminal repeat. Taken together, these findings indicate a novel antiviral mechanism mediated by the influx of soluble X‐ DING ‐ CD 4, its signaling to promote self‐amplification, and functional duality as an endogenous innate immunity effector and exogenous factor regulating gene expression in bystander cells.