title: High glucose enhances HIV entry into T cells through upregulation of CXCR4.
abstract: It is well known that patients with HIV are prone to diabetes mellitus because of the side effects of HARRT. However, whether high glucose affects the HIV infection of T cells is not clear. Recent studies have shown that upregulation of GLUT-1 renders T cells susceptible to HIV infection. We hypothesized that hyperglycemia has the potential to increase HIV infection by enhancing its entry into immune cells. The effect of high glucose on HIV entry into T cells (Jurkat cells and PBMCs) and the mechanisms involved were investigated. High glucose significantly enhanced HIV entry, which was associated with increased T-cell expression of CXCR4. However, T cells with silenced HIF-1α displayed attenuated expression of CXCR4, whereas T cells with silenced CXCR4 showed decreased HIV entry in a high-glucose milieu. On the one hand, high glucose stimulated T-cell ROS generation, and H(2)O(2) at low concentrations enhanced the entry of HIV into T cells. On the other hand, inhibition of ROS not only attenuated high-glucose-mediated T-cell expression of CXCR4 and HIF-1α but also mitigated T-cell HIV entry in a high-glucose milieu. In our study, high glucose enhanced HIV entry into T cells by increasing expression of CXCR4 and HIF-1α.
authors.affiliation: 1.North Shore University Hospital, 100 Community Drive, Great Neck, NY 11021; E-mail psinghal@nshs.edu.
authors.forename: Xiqian
authors.initials: X
authors.lastname: Lan
authors.forename: Kang
authors.initials: K
authors.lastname: Cheng
authors.forename: Nirupama
authors.initials: N
authors.lastname: Chandel
authors.forename: Rivka
authors.initials: R
authors.lastname: Lederman
authors.forename: Aakash
authors.initials: A
authors.lastname: Jhaveri
authors.forename: Mohammad
authors.initials: M
authors.lastname: Husain
authors.forename: Ashwani
authors.initials: A
authors.lastname: Malhotra
authors.forename: Pravin C
authors.initials: PC
authors.lastname: Singhal
mesh_terms: D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D020868:Gene Silencing / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D019169:Jurkat Cells; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000821:virology*; D015854:Up-Regulation / Q000187:drug effects*; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: C527276:CXCR4 protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D019718:Receptors, CXCR4; D006861:Hydrogen Peroxide; D005947:Glucose
keywords: HIF-1α; Jurkat cells; LTR; ROS; antioxidants; enzymes; receptors
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