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PMID: 1727486 Published · ppublish English Journal Article

Human immunodeficiency virus type 1 Vpu protein regulates the formation of intracellular gp160-CD4 complexes.

Journal of virology ·Vol. 66 ·No. 1 ·1992-01-00 ·Pages 226-34

Willey RL, Maldarelli F, Martin MA, Strebel K

Abstract

Intracellular transport and processing of the human immunodeficiency virus type 1 (HIV-1) envelope precursor glycoprotein, gp160, proceeds via the endoplasmic reticulum and Golgi complex and involves proteolytic processing of gp160 into the mature virion components, gp120 and gp41. We found that coexpression of gp160 and human CD4 in HeLa cells severely impaired gp120 production due to the formation of intracellular gp160-CD4 complexes. This CD4-mediated inhibition of gp160 processing was alleviated by coexpression of the HIV-1-encoded Vpu protein. The coexpression of Vpu and CD4 in the presence of gp160 resulted in increased degradation of CD4. Although the precise mechanism(s) responsible for the Vpu effect is presently unclear, our findings suggest that Vpu may destabilize intracellular gp160-CD4 complexes.

MeSH Terms
CD4 Antigens/metabolism Gene Products, env/metabolism HIV Envelope Protein gp160 HIV-1/metabolism HeLa Cells Human Immunodeficiency Virus Proteins Humans Precipitin Tests Protein Precursors/metabolism Protein Processing, Post-Translational Transfection Viral Regulatory and Accessory Proteins/metabolism
Chemicals
CD4 Antigens Gene Products, env HIV Envelope Protein gp160 Human Immunodeficiency Virus Proteins Protein Precursors Viral Regulatory and Accessory Proteins vpu protein, Human immunodeficiency virus 1
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Willey R L
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Maldarelli F
Martin M A
Strebel K
References (30)
30 references, click to expand
  1. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV.
    Nature. 1984 Dec 20-1985 Jan 2;312(5996):767-8 PMID: 6083454
  2. A novel gene of HIV-1, vpu, and its 16-kilodalton product.
    Science. 1988 Sep 2;241(4870):1221-3 PMID: 3261888
  3. Downregulation of cell surface molecules during noncytopathic infection of T cells with human immunodeficiency virus.
    J Virol. 1987 Dec;61(12):3741-8 PMID: 3500327
  4. Intracellular processing of the gp160 HIV-1 envelope precursor. Endoproteolytic cleavage occurs in a cis or medial compartment of the Golgi complex.
    J Biol Chem. 1990 Feb 15;265(5):2640-9 PMID: 2406237
  5. Prevention of HIV-1 glycoprotein transport by soluble CD4 retained in the endoplasmic reticulum.
    Nature. 1990 Jun 14;345(6276):625-8 PMID: 2190096
  6. HIV-2 link to AIDS in West Africa.
    J Acquir Immune Defic Syndr. 1990;3(3):220-30 PMID: 2406413
  7. The human immunodeficiency virus type 1-specific protein vpu is required for efficient virus maturation and release.
    J Virol. 1990 Feb;64(2):621-9 PMID: 2404139
  8. High concentrations of recombinant soluble CD4 are required to neutralize primary human immunodeficiency virus type 1 isolates.
    Proc Natl Acad Sci U S A. 1990 Sep;87(17):6574-8 PMID: 2395859
  9. HIV requires multiple gp120 molecules for CD4-mediated infection.
    Nature. 1990 Jul 19;346(6281):277-9 PMID: 2374593
  10. The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection.
    Proc Natl Acad Sci U S A. 1982 Nov;79(22):6777-81 PMID: 6294651
  11. A new technique for the assay of infectivity of human adenovirus 5 DNA.
    Virology. 1973 Apr;52(2):456-67 PMID: 4705382
  12. Mutations within the human immunodeficiency virus type 1 gp160 envelope glycoprotein alter its intracellular transport and processing.
    Virology. 1991 Sep;184(1):319-29 PMID: 1871974
  13. Structural characteristics of the M2 protein of influenza A viruses: evidence that it forms a tetrameric channel.
    Virology. 1991 Feb;180(2):617-24 PMID: 1989386
  14. Specific structural alteration of the influenza haemagglutinin by amantadine.
    EMBO J. 1990 Nov;9(11):3469-76 PMID: 2209554
  15. Envelope glycoproteins from biologically diverse isolates of immunodeficiency viruses have widely different affinities for CD4.
    Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):512-6 PMID: 1899141
  16. Perturbation of host-cell membrane is a primary mechanism of HIV cytopathology.
    Virology. 1991 Apr;181(2):500-11 PMID: 1901681
  17. Direct measurement of soluble CD4 binding to human immunodeficiency virus type 1 virions: gp120 dissociation and its implications for virus-cell binding and fusion reactions and their neutralization by soluble CD4.
    J Virol. 1991 Mar;65(3):1133-40 PMID: 1995942
  18. CD4 is retained in the endoplasmic reticulum by the human immunodeficiency virus type 1 glycoprotein precursor.
    J Virol. 1990 Nov;64(11):5585-93 PMID: 2214026
  19. Env and Vpu proteins of human immunodeficiency virus type 1 are produced from multiple bicistronic mRNAs.
    J Virol. 1990 Nov;64(11):5448-56 PMID: 2214021
  20. The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain.
    Cell. 1986 Nov 7;47(3):333-48 PMID: 3094962
  21. Depletion of the surface CD4 molecule by the envelope protein of human immunodeficiency virus expressed in a human CD4+ monocytoid cell line.
    J Virol. 1989 Sep;63(9):3748-54 PMID: 2788223
  22. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus.
    Nature. 1984 Dec 20-1985 Jan 2;312(5996):763-7 PMID: 6096719
  23. Biosynthesis and processing of human immunodeficiency virus type 1 envelope glycoproteins: effects of monensin on glycosylation and transport.
    J Virol. 1989 Jun;63(6):2452-6 PMID: 2542563
  24. Biosynthesis, cleavage, and degradation of the human immunodeficiency virus 1 envelope glycoprotein gp160.
    Proc Natl Acad Sci U S A. 1988 Dec;85(24):9580-4 PMID: 2849111
  25. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone.
    J Virol. 1986 Aug;59(2):284-91 PMID: 3016298
  26. Alterations in T4 (CD4) protein and mRNA synthesis in cells infected with HIV.
    Science. 1986 Nov 28;234(4780):1123-7 PMID: 3095925
  27. The HIV 'A' (sor) gene product is essential for virus infectivity.
    Nature. 1987 Aug 20-26;328(6132):728-30 PMID: 2441266
  28. Trans-activation of the human immunodeficiency virus long terminal repeat sequence by DNA viruses.
    Proc Natl Acad Sci U S A. 1986 Dec;83(24):9759-63 PMID: 2432602
  29. Molecular and biochemical analyses of human immunodeficiency virus type 1 vpu protein.
    J Virol. 1989 Sep;63(9):3784-91 PMID: 2788224
  30. A soluble form of CD4 (T4) protein inhibits AIDS virus infection.
    Nature. 1988 Jan 7;331(6151):82-4 PMID: 3257544
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.66.1.226-234.1992
Published
1992-01-00
Pages
226-34
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC238279
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.66.1.226-234.1992 PMC Full Text View journal details
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