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HIV-1 matrix dependent membrane targeting is regulated by Gag mRNA trafficking

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).

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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.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Jin, J
Sturgeon, Tsturgeon@pitt.eduSTURGEON
Weisz, OAweisz@pitt.eduWEISZ
Mothes, W
Montelaro, RCrmont@pitt.eduRMONT
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorHarris, Reuben S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 7 August 2009
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 4
Number: 8
DOI or Unique Handle: 10.1371/journal.pone.0006551
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
School of Medicine > Cell Biology and Molecular Physiology
Refereed: Yes
MeSH Headings: Fluorescence; Gene Products, gag--genetics; HIV-1--genetics; HIV-1--physiology; Hepatitis B virus--genetics; Humans; Membrane Fusion; Protein Transport; RNA Processing, Post-Transcriptional; RNA, Messenger--genetics; Viral Matrix Proteins--metabolism
PubMed Central ID: PMC2717210
PubMed ID: 19662089
Date Deposited: 03 Aug 2012 16:09
Last Modified: 04 Feb 2019 15:57
URI: http://d-scholarship.pitt.edu/id/eprint/13162

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