CAMP Signaling Enhances HIV-1 Long Terminal Repeat (LTR)-directed Transcription and Viral Replication in Bone Marrow Progenitor Cells. (9th March 2017)

• Record Type: Journal Article
• Authors: Banerjee, Anupam; Li, Luna; Pirrone, Vanessa; Krebs, Fred C; Wigdahl, Brian; Nonnemacher, Michael R
• Is Part Of: Clinical medicine insights. Volume 10(2017)
• Publication Date: 2017-03-09
• Subjects: HIV-1 -- cAMP -- CREB -- PKA -- CXCR4; Pathology -- Periodicals; Pathology; Pathology; Pathology; Electronic journals; Periodicals; Fulltext; Internet Resources; Periodicals; Periodicals; 616.0705
• DOI: 10.1177/1179555717694535
• Languages: English
• ISSNs: 1179-5557

Abstract

CD34 + hematopoietic progenitor cells have been shown to be susceptible to HIV-1 infection, possibly due to a low-level expression of CXCR4, a coreceptor for HIV-1 entry. Given these observations, we have explored the impact of forskolin on cell surface expression of CXCR4 in a cell line model (TF-1). The elevation of intracellular cyclic adenosine monophosphate (cAMP) by forskolin through adenylyl cyclase (AC) resulted in transcriptional upregulation of CXCR4 with a concomitant increase in replication of the CXCR4-utilizing HIV-1 strain IIIB. Transient expression analyses also demonstrated an increase in CXCR4-, CCR5-, and CXCR4-/CCR5-utilizing HIV-1 (LAI, YU2, and 89.6, respectively) promoter activity. Studies also implicated the protein kinase A (PKA) pathway and the downstream transcription factor CREB-1 in interfacing with cAMP response elements located in the CXCR4 and viral promoter. These observations suggest that the cAMP signaling pathway may serve as a regulator of CXCR4 levels and concomitantly of HIV-1 replication in bone marrow (BM) progenitor cells.