| Dynamin 2 is required for the enhancement of HIV-1 infectivity by Nef. | |
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MedLine Citation:
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PMID: 17412836 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Nef is a virulence factor of HIV-1 and other primate lentiviruses that is crucial for rapid progression to AIDS. In cell culture, Nef increases the infectivity of HIV-1 progeny virions by an unknown mechanism. We now show that dynamin 2 (Dyn2), a key regulator of vesicular trafficking, is a binding partner of Nef that is required for its ability to increase viral infectivity. Dominant-negative Dyn2 or the depletion of Dyn2 by small interfering RNA potently inhibited the effect of Nef on HIV-1 infectivity. Furthermore, in Dyn2-depleted cells, this function of Nef could be rescued by ectopically expressed Dyn2 but not by Dyn1, a closely related isoform that does not bind Nef. The infectivity enhancement by Nef also depended on clathrin, because it was diminished in clathrin-depleted cells and profoundly inhibited in cells expressing the clathrin-binding domain of AP180, which blocks clathrin-coated pit formation but not clathrin-independent endocytosis. Together, these findings imply that the infectivity enhancement activity of Nef depends on Dyn2- and clathrin-mediated membrane invagination events. |
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Authors:
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Massimo Pizzato; Anna Helander; Elena Popova; Arianna Calistri; Alessia Zamborlini; Giorgio Palù; Heinrich G Göttlinger |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2007-04-05 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 104 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2007 Apr |
Date Detail:
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Created Date: 2007-04-18 Completed Date: 2007-06-06 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 6812-7 Citation Subset: IM |
Affiliation:
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Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA. m.pizzato@imperial.ac.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals COS Cells Cell Line Cell Membrane / metabolism, virology Cercopithecus aethiops Dynamin II / physiology* Gene Products, nef / deficiency, genetics, physiology* HIV Infections / metabolism HIV-1 / pathogenicity*, physiology Humans Jurkat Cells Protein Binding / physiology Virion / pathogenicity, physiology nef Gene Products, Human Immunodeficiency Virus |
| Grant Support | |
ID/Acronym/Agency:
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AI29873/AI/NIAID NIH HHS; AI54261/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Gene Products, nef; 0/nef Gene Products, Human Immunodeficiency Virus; 0/nef protein, Human immunodeficiency virus 1; EC 3.6.5.5/Dynamin II |
| Comments/Corrections | |
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