eprintid: 13162 rev_number: 27 userid: 677 importid: 470 dir: disk0/00/01/31/62 datestamp: 2012-08-03 16:09:41 lastmod: 2019-02-04 15:57:43 status_changed: 2012-08-03 16:09:41 type: article metadata_visibility: show contact_email: rmont@pitt.edu item_issues_count: 0 eprint_status: archive creators_name: Jin, J creators_name: Sturgeon, T creators_name: Weisz, OA creators_name: Mothes, W creators_name: Montelaro, RC creators_email: creators_email: sturgeon@pitt.edu creators_email: weisz@pitt.edu creators_email: creators_email: rmont@pitt.edu creators_id: creators_id: STURGEON creators_id: WEISZ creators_id: creators_id: RMONT contributors_type: http://www.loc.gov/loc.terms/relators/EDT contributors_name: Harris, Reuben S. title: HIV-1 matrix dependent membrane targeting is regulated by Gag mRNA trafficking ispublished: pub divisions: sch_gsph_infectiousdiseasesmicrobiology divisions: sch_med_cellbiologyandmolecularphysiology full_text_status: public abstract: Retroviral Gag polyproteins are necessary and sufficient for virus budding. Productive HIV-1 Gag assembly takes place at the plasma membrane. However, little is known about the mechanisms by which thousands of Gag molecules are targeted to the plasma membrane. Using a bimolecular fluorescence complementation (BiFC) assay, we recently reported that the cellular sites and efficiency of HIV-1 Gag assembly depend on the precise pathway of Gag mRNA export from the nucleus, known to be mediated by Rev. Here we describe an assembly deficiency in human cells for HIV Gag whose expression depends on hepatitis B virus (HBV) post-transcriptional regulatory element (PRE) mediated-mRNA nuclear export. PRE-dependent HIV Gag expressed well in human cells, but assembled with slower kinetics, accumulated intracellularly, and failed to associate with a lipid raft compartment where the wild-type Rev-dependent HIV-1 Gag efficiently assembles. Surprisingly, assembly and budding of PRE-dependent HIV Gag in human cells could be rescued in trans by co-expression of Rev-dependent Gag that provides correct membrane targeting signals, or in cis by replacing HIV matrix (MA) with other membrane targeting domains. Taken together, our results demonstrate deficient membrane targeting of PRE-dependent HIV-1 Gag and suggest that HIV MA function is regulated by the trafficking pathway of the encoding mRNA. © 2009 Jin et al. date: 2009-08-07 date_type: published publication: PLoS ONE volume: 4 number: 8 refereed: TRUE id_number: 10.1371/journal.pone.0006551 pmcid: PMC2717210 pmid: 19662089 mesh_headings: Fluorescence mesh_headings: Gene Products, gag--genetics mesh_headings: HIV-1--genetics mesh_headings: HIV-1--physiology mesh_headings: Hepatitis B virus--genetics mesh_headings: Humans mesh_headings: Membrane Fusion mesh_headings: Protein Transport mesh_headings: RNA Processing, Post-Transcriptional mesh_headings: RNA, Messenger--genetics mesh_headings: Viral Matrix Proteins--metabolism chemical_names: Gene Products, gag chemical_names: RNA, Messenger chemical_names: Viral Matrix Proteins citation: Jin, J and Sturgeon, T and Weisz, OA and Mothes, W and Montelaro, RC (2009) HIV-1 matrix dependent membrane targeting is regulated by Gag mRNA trafficking. PLoS ONE, 4 (8). document_url: http://d-scholarship-dev.library.pitt.edu/13162/1/HIV-1_Matrix.pdf document_url: http://d-scholarship-dev.library.pitt.edu/13162/8/licence.txt