title: The interplay between the X-DING-CD4, IFN-α and IL-8 gene activity in quiescent and mitogen- or HIV-1-exposed PBMCs from HIV-1 elite controllers, AIDS progressors and HIV-negative controls.
abstract: X-DING-CD4 blocks HIV-1 long terminal repeat (LTR) and pathogen induced pro-inflammatory response. Increased activity of the X-DING-CD4 gene is associated with cellular resistance to virus; therefore, HIV-1 elite controllers (ECs) should have higher X-DING-CD4 and reduced pro-inflammatory mRNA activity than viremic or uninfected individuals. Also, depending on the cell stimulating factor, expression of X-DING-CD4 mRNA in ECs might be autonomous or contingent on IFN signaling. We compared expression of X-DING-CD4, IFN-α and IL-8 mRNAs in naive, phytohemagglutinin- or HIV-1 exposed PBMCs from ECs, HIV progressors and negative controls; tested correlation between X-DING-CD4 and IFN-α expression; sensitivity of the X-DING-CD4 gene to IFN-α regulation; and evaluated interactions between innate and pro-inflammatory genes. We found that expression of X-DING-CD4 and IFN-α was up-regulated in ECs and correlated in cells stimulated with mitogen, but not HIV-1. The X-DING-CD4 gene was more sensitive to HIV-1 than rIFN-α stimulation. ECs had significantly less IL-8 mRNA when PBMCs were exposed to exogenous HIV-1. Two-way ANOVA showed that control of HIV-1 and virus-induced pro-inflammatory response by ECs stemmed from interactions between expression of innate immunity and pro-inflammatory genes, the state of cell stimulation and the status of virus control. Consequently, interaction of multiple host innate immune responses rather than a single mechanism regulates restriction of HIV-1 in ECs.
authors.affiliation: Protein Chemistry Laboratory, St. Luke's-Roosevelt Institute for Health Sciences, Columbia University, NY, USA.
authors.forename: Rakhee
authors.initials: R
authors.lastname: Sachdeva
authors.forename: Rasheda Y
authors.initials: RY
authors.lastname: Shilpi
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Simm
mesh_terms: D018791:CD4 Lymphocyte Count; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D018450:Disease Progression; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000276:immunology*; D018023:HIV Seronegativity; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism*; D016898:Interferon-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation; D010835:Phytohemagglutinins / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D020239:Receptor Cross-Talk
chemical_list: D002352:Carrier Proteins; D018836:Inflammation Mediators; D016898:Interferon-alpha; D016209:Interleukin-8; D010835:Phytohemagglutinins; D012333:RNA, Messenger; C544193:X-DING-CD4 protein, human
keywords: DING protein; HIV-1 restriction; IFN-α; X-DING-CD4; elite HIV-1 controllers; innate immunity