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PMID: 19286658 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Intracellular transport of human immunodeficiency virus type 1 genomic RNA and viral production are dependent on dynein motor function and late endosome positioning.

The Journal of biological chemistry ·Vol. 284 ·No. 21 ·2009-05-22 ·Pages 14572-85

Lehmann M, Milev MP, Abrahamyan L, Yao XJ, Pante N, Mouland AJ

Abstract

Our earlier work indicated that the human immunodeficiency virus type 1 (HIV-1) genomic RNA (vRNA) is trafficked to the microtubule-organizing center (MTOC) when heterogeneous nuclear ribonucleoprotein A2/B1 is depleted from cells. Also, Rab7-interacting lysosomal protein promoted dynein motor complex, late endosome and vRNA clustering at the MTOC suggesting that the dynein motor and late endosomes were involved in vRNA trafficking. To investigate the role of the dynein motor in vRNA trafficking, dynein motor function was disrupted by small interference RNA-mediated depletion of the dynein heavy chain or by p50/dynamitin overexpression. These treatments led to a marked relocalization of vRNA and viral structural protein Gag to the cell periphery with late endosomes and a severalfold increase in HIV-1 production. In contrast, rerouting vRNA to the MTOC reduced virus production. vRNA localization depended on Gag membrane association as shown using both myristoylation and Gag nucleocapsid domain proviral mutants. Furthermore, the cytoplasmic localization of vRNA and Gag was not attributable to intracellular or internalized endocytosed virus particles. Our results demonstrate that dynein motor function is important for regulating Gag and vRNA egress on endosomal membranes in the cytoplasm to directly impact on viral production.

MeSH Terms
Amino Acid Sequence Biological Transport Dyneins/metabolism Endocytosis Endosomes/metabolism,ultrastructure,virology Gene Products, gag/chemistry,metabolism Genome, Viral/genetics HIV-1/genetics,ultrastructure HeLa Cells Human Immunodeficiency Virus Proteins/metabolism Humans Intracellular Membranes/metabolism,ultrastructure,virology Intracellular Space/metabolism,ultrastructure,virology Lysosomal-Associated Membrane Protein 1/metabolism Molecular Sequence Data Myristic Acid/metabolism RNA, Viral/metabolism Viral Regulatory and Accessory Proteins/metabolism Virion/metabolism Virus Assembly
Chemicals
Gene Products, gag Human Immunodeficiency Virus Proteins Lysosomal-Associated Membrane Protein 1 RNA, Viral Viral Regulatory and Accessory Proteins vpu protein, Human immunodeficiency virus 1 Myristic Acid Dyneins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Lehmann Martin
HIV-1 RNA Trafficking Laboratory, Lady Davis Institute for Medical Research, Quebec.
Milev Miroslav P
Abrahamyan Levon
Yao Xiao-Jian
Pante Nelly
Mouland Andrew J
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
DOI
10.1074/jbc.M808531200
Published
2009-05-22
Epub
2009-00-13
Pages
14572-85
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2682905
Subset
IM
External Links
PubMed source DOI: 10.1074/jbc.M808531200 PMC Full Text View journal details
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