Home LiteratureArticle Details
PMID: 17108041 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Selective restriction of Nef-defective human immunodeficiency virus type 1 by a proteasome-dependent mechanism.

Journal of virology ·Vol. 81 ·No. 3 ·2007-02-00 ·Pages 1534-6

Qi M, Aiken C

Abstract

The Nef protein enhances human immunodeficiency virus type 1 (HIV-1) infectivity by facilitating an early postentry step in the virus life cycle. We report here that the addition of MG132 or lactacystin, each a specific inhibitor of cellular proteasome activity, preferentially enhances cellular permissiveness to infection by Nef-defective versus wild-type HIV-1. Pseudotyping by the glycoprotein of vesicular stomatitis virus rendered Nef-defective HIV-1 particles minimally responsive to the enhancing effects of proteasome inhibitors. These results suggest that Nef enhances the infectivity of HIV-1 particles by reducing their susceptibility to proteasomal degradation in target cells.

MeSH Terms
Cysteine Endopeptidases/metabolism,pharmacology Gene Products, nef/genetics,physiology HIV-1/drug effects,genetics,physiology Humans Proteasome Endopeptidase Complex nef Gene Products, Human Immunodeficiency Virus
Chemicals
Gene Products, nef nef Gene Products, Human Immunodeficiency Virus Cysteine Endopeptidases Proteasome Endopeptidase Complex
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Qi Mingli
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232-2363, USA.
Aiken Christopher
References (29)
29 references, click to expand
  1. Identification of the Nef-associated kinase as p21-activated kinase 2.
    Curr Biol. 1999 Dec 2;9(23):1407-10 PMID: 10607567
  2. Human immunodeficiency virus type 1 Nef protein is incorporated into virus particles and specifically cleaved by the viral proteinase.
    Virology. 1996 May 1;219(1):228-36 PMID: 8623533
  3. Nef increases infectivity of HIV via lipid rafts.
    Curr Biol. 2001 Jun 5;11(11):875-9 PMID: 11516650
  4. Nef increases the synthesis of and transports cholesterol to lipid rafts and HIV-1 progeny virions.
    Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8460-5 PMID: 12824470
  5. Producer-cell modification of human immunodeficiency virus type 1: Nef is a virion protein.
    J Virol. 1996 Jul;70(7):4283-90 PMID: 8676450
  6. Human immunodeficiency virus type 1 Nef associates with a member of the p21-activated kinase family.
    J Virol. 1996 Sep;70(9):6157-61 PMID: 8709241
  7. Nef association with human immunodeficiency virus type 1 virions and cleavage by the viral protease.
    J Virol. 1997 Feb;71(2):1013-8 PMID: 8995620
  8. Pseudotyping human immunodeficiency virus type 1 (HIV-1) by the glycoprotein of vesicular stomatitis virus targets HIV-1 entry to an endocytic pathway and suppresses both the requirement for Nef and the sensitivity to cyclosporin A.
    J Virol. 1997 Aug;71(8):5871-7 PMID: 9223476
  9. Infectivity enhancement by HIV-1 Nef is dependent on the pathway of virus entry: implications for HIV-based gene transfer systems.
    Virology. 1998 Feb 15;241(2):224-33 PMID: 9499797
  10. Antiviral activity of the proteasome on incoming human immunodeficiency virus type 1.
    J Virol. 1998 May;72(5):3845-50 PMID: 9557668
  11. Virion incorporation of human immunodeficiency virus type 1 Nef is mediated by a bipartite membrane-targeting signal: analysis of its role in enhancement of viral infectivity.
    J Virol. 1998 Nov;72(11):8833-40 PMID: 9765428
  12. Association of Nef with the human immunodeficiency virus type 1 core.
    J Virol. 1999 Oct;73(10):8824-30 PMID: 10482638
  13. Inhibition of lysosome and proteasome function enhances human immunodeficiency virus type 1 infection.
    J Virol. 2005 May;79(9):5705-12 PMID: 15827185
  14. Functional characterization of HIV-1 Nef mutants in the context of viral infection.
    Virology. 2006 Aug 1;351(2):322-39 PMID: 16684552
  15. Nef does not affect the efficiency of human immunodeficiency virus type 1 fusion with target cells.
    J Virol. 2003 Oct;77(19):10645-50 PMID: 12970449
  16. The membrane-proximal tyrosine-based sorting signal of human immunodeficiency virus type 1 gp41 is required for optimal viral infectivity.
    J Virol. 2004 Feb;78(3):1069-79 PMID: 14722262
  17. Disruption of the actin cytoskeleton can complement the ability of Nef to enhance human immunodeficiency virus type 1 infectivity.
    J Virol. 2004 Jun;78(11):5745-55 PMID: 15140972
  18. HIV-1 Nef enhances both membrane expression and virion incorporation of Env products. A model for the Nef-dependent increase of HIV-1 infectivity.
    J Biol Chem. 2004 May 28;279(22):22996-3006 PMID: 15033985
  19. HIV-1 virion fusion assay: uncoating not required and no effect of Nef on fusion.
    Virology. 2004 Oct 10;328(1):36-44 PMID: 15380356
  20. A second origin of DNA plus-strand synthesis is required for optimal human immunodeficiency virus replication.
    J Virol. 1992 May;66(5):2814-20 PMID: 1560526
  21. Packaging system for rapid production of murine leukemia virus vectors with variable tropism.
    J Virol. 1992 Aug;66(8):5110-3 PMID: 1321291
  22. The human immunodeficiency virus-1 nef gene product: a positive factor for viral infection and replication in primary lymphocytes and macrophages.
    J Exp Med. 1994 Jan 1;179(1):101-13 PMID: 8270859
  23. Optimal infectivity in vitro of human immunodeficiency virus type 1 requires an intact nef gene.
    J Virol. 1994 May;68(5):2906-14 PMID: 8151761
  24. Expression of the human immunodeficiency virus type 1 (HIV-1) nef gene during HIV-1 production increases progeny particle infectivity independently of gp160 or viral entry.
    J Virol. 1995 Jan;69(1):579-84 PMID: 7983759
  25. Generation of high-titer pseudotyped retroviral vectors with very broad host range.
    Methods Cell Biol. 1994;43 Pt A:99-112 PMID: 7823872
  26. Human immunodeficiency virus type 1 Nef increases the efficiency of reverse transcription in the infected cell.
    J Virol. 1995 Jul;69(7):4053-9 PMID: 7539505
  27. Nef stimulates human immunodeficiency virus type 1 proviral DNA synthesis.
    J Virol. 1995 Aug;69(8):5048-56 PMID: 7541845
  28. The growth advantage conferred by HIV-1 nef is determined at the level of viral DNA formation and is independent of CD4 downregulation.
    Virology. 1995 Oct 1;212(2):451-7 PMID: 7571414
  29. Human immunodeficiency virus type 1 particles pseudotyped with envelope proteins that fuse at low pH no longer require Nef for optimal infectivity.
    J Virol. 2001 Apr;75(8):4014-8 PMID: 11264394
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
Published
2007-02-00
Epub
2006-00-15
Pages
1534-6
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC1797497
Subset
IM
Grants
NIAID NIH HHS · R01 AI040364 · United States
NIAID NIH HHS · AI40364 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]