The HIV-1 matrix protein does not interact directly with the protein interactive domain of AP-3 delta

• Type of Material: Article
• Authors: Sampson K. Kyere, University of Maryland; Peter Y. Mercredi, University of Maryland; Xinhong Dong, Emory University; Paul Spearman, Emory University; Michael F. Summers, University of Maryland
• Language: English
• Date: 2012-11-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier B.V. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.virusres.2012.06.007
• Title of Journal or Parent Work: Virus Research
• ISSN: 0168-1702
• Volume: 169
• Issue: 2
• Start Page: 411
• End Page: 414
• Keywords: CELL-CELL SPREAD; HUMAN-IMMUNODEFICIENCY-VIRUS; LIPID RAFTS; GAG; Life Sciences & Biomedicine; Retrovirus; PRIMARY MACROPHAGES; ENVELOPE GLYCOPROTEIN; INFECTIOUS HIV-1; Gag trafficking; INTRACELLULAR TRAFFICKING; PLASMA-MEMBRANE; HIV-1; Science & Technology; Virology; Gag assembly; REPLICATION
• Research Categories: Health Sciences, Epidemiology; Biology, Virology; Health Sciences, Immunology

Abstract

During the late phase of the Human Immunodeficiency Virus Type-1 (HIV-1) replication cycle, viral Gag proteins and the intact RNA genome are trafficked to specific sub-cellular membranes where virus assembly and budding occurs. Targeting to the plasma membranes of T cells and macrophages is mediated by interactions between the N-terminal matrix (MA) domain of Gag and cellular phosphatidylinositol-4,5-bisphosphate [PI(4,5)P 2 ] molecules. However, in macrophages and dendritic cells, a subset of Gag proteins appears to be targeted to tetraspanin enriched viral compartments, a process that appears to be mediated by MA interactions with the Delta subunit of the cellular Adaptor Protein AP-3 (AP-3δ). We cloned, overexpressed and purified the protein interactive domain of AP-3δ and probed for MA binding by NMR. Unexpectedly, no evidence of binding was observed in these in vitro experiments, even at relatively high protein concentrations (200μM), suggesting that AP-3δ plays an alternative role in HIV-1 assembly.