title: Human X-DING-CD4 mediates resistance to HIV-1 infection through novel paracrine-like signaling.
abstract: X-DING-CD4 is a novel phosphatase mediating antiviral responses to HIV-1 infection. This protein is constitutively expressed and secreted by HIV-1 resistant CD4(+) T cells and its mRNA transcription is up-regulated in peripheral blood mononuclear cells from HIV-1 elite controllers. The secreted/soluble X-DING-CD4 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-CD4 enters cells by endocytosis and that influx of this protein induced transcription of interferon-α and endogenous X-DING-CD4 mRNA in transformed CD4(+) T cells and primary macrophages. Treatment of HIV-1 susceptible cells with exogenous X-DING-CD4 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-CD4, its signaling to promote self-amplification, and functional duality as an endogenous innate immunity effector and exogenous factor regulating gene expression in bystander cells.
authors.affiliation: Protein Chemistry Laboratory, St Luke's/Roosevelt Institute for Health Sciences, Columbia University, New York, NY, USA.
authors.forename: Rakhee
authors.initials: R
authors.lastname: Sachdeva
authors.forename: Yuchang
authors.initials: Y
authors.lastname: Li
authors.forename: Rasheda Y
authors.initials: RY
authors.lastname: Shilpi
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Simm
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004705:Endocytosis; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000378:metabolism*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000821:virology; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation
chemical_list: D002352:Carrier Proteins; D016898:Interferon-alpha; D016328:NF-kappa B; C544193:X-DING-CD4 protein, human
keywords: DING protein; HIV-1; antiviral factor; cellular resistance; transcription inhibition