Home LiteratureArticle Details
PMID: 8416370 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Mutations in the cytoplasmic domain of human immunodeficiency virus type 1 transmembrane protein impair the incorporation of Env proteins into mature virions.

Journal of virology ·Vol. 67 ·No. 1 ·1993-01-00 ·Pages 213-21

Yu X, Yuan X, McLane MF, Lee TH, Essex M

Abstract

In-frame stop codons were introduced into the coding region of human immunodeficiency virus type 1 (HIV-1) transmembrane protein (gp41). Truncation of 147 amino acids from the carboxyl terminus of gp41 (TM709) significantly decreased the stability and cell surface expression of the viral Env proteins, while truncation of 104 amino acids (TM752) did not. Truncation of 43 or more amino acids from the carboxyl terminus of gp41 generated mutant viruses which were noninfectious in several human CD4+ T lymphoid cell lines and fresh peripheral blood mononuclear cells. Analysis of the noninfectious mutant virions revealed significantly reduced incorporation of the Env proteins compared with the wild-type virions. Comparable amounts of Env proteins were detected on the surfaces of wild-type- and TM752-transfected cells, suggesting that the structures of gp41 required for efficient incorporation of Env proteins were disrupted in mutant TM752. Truncation of the last 12 amino acids (TM844) from the carboxyl terminus of gp41 did not significantly affect the assembly and release of virions or the incorporation of Env proteins into mature virions. However, the TM844 virus had dramatically decreased infectivity compared with the wild-type virus. This suggests that the cytoplasmic domain of gp41 also plays a role in other steps of virus replication.

MeSH Terms
Animals Antibodies, Monoclonal Base Sequence Biological Transport Cell Line Codon DNA Mutational Analysis Fluorescent Antibody Technique Gene Products, env/metabolism HIV Envelope Protein gp120/immunology HIV Envelope Protein gp41/genetics,immunology,isolation & purification HIV-1/genetics,growth & development,metabolism,pathogenicity Membrane Proteins/metabolism Molecular Sequence Data Mutagenesis Protein Processing, Post-Translational Terminator Regions, Genetic/genetics Transfection Virion/growth & development,metabolism Virulence
Chemicals
Antibodies, Monoclonal Codon Gene Products, env HIV Envelope Protein gp120 HIV Envelope Protein gp41 Membrane Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Yu X
Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts 02115.
Yuan X
McLane M F
Lee T H
Essex M
References (53)
53 references, click to expand
  1. Analysis of a human immunodeficiency virus type 1 isolate carrying a truncated transmembrane glycoprotein.
    Virology. 1992 Aug;189(2):534-46 PMID: 1322587
  2. Alphavirus spike-nucleocapsid interaction and network antibodies.
    J Virol. 1992 Aug;66(8):5106-9 PMID: 1629965
  3. Genome organization and transactivation of the human immunodeficiency virus type 2.
    Nature. 1987 Apr 16-22;326(6114):662-9 PMID: 3031510
  4. The genome organization of STLV-3 is similar to that of the AIDS virus except for a truncated transmembrane protein.
    Cell. 1987 May 8;49(3):307-19 PMID: 3646094
  5. A short sequence in the COOH-terminus makes an adenovirus membrane glycoprotein a resident of the endoplasmic reticulum.
    Cell. 1987 Jul 17;50(2):311-7 PMID: 2954653
  6. Sequence of simian immunodeficiency virus from macaque and its relationship to other human and simian retroviruses.
    Nature. 1987 Aug 6-12;328(6130):543-7 PMID: 3649576
  7. Mutants of the Rous sarcoma virus envelope glycoprotein that lack the transmembrane anchor and cytoplasmic domains: analysis of intracellular transport and assembly into virions.
    J Virol. 1987 Oct;61(10):2981-8 PMID: 3041017
  8. Functional regions of the envelope glycoprotein of human immunodeficiency virus type 1.
    Science. 1987 Sep 11;237(4820):1351-5 PMID: 3629244
  9. Sequence of simian immunodeficiency virus from African green monkey, a new member of the HIV/SIV group.
    Nature. 1988 Jun 2;333(6172):457-61 PMID: 3374586
  10. Spike--nucleocapsid interaction in Semliki Forest virus reconstructed using network antibodies.
    Nature. 1988 Nov 3;336(6194):36-42 PMID: 2460771
  11. Expression of the human immunodeficiency virus envelope glycoprotein is restricted to basolateral surfaces of polarized epithelial cells.
    J Virol. 1989 Feb;63(2):978-82 PMID: 2536121
  12. Theoretically determined three-dimensional structures for amphipathic segments of the HIV-1 gp41 envelope protein.
    AIDS Res Hum Retroviruses. 1989 Feb;5(1):7-22 PMID: 2541749
  13. Glycoprotein cytoplasmic domain sequences required for rescue of a vesicular stomatitis virus glycoprotein mutant.
    J Virol. 1989 Sep;63(9):3569-78 PMID: 2547986
  14. A general model for the transmembrane proteins of HIV and other retroviruses.
    AIDS Res Hum Retroviruses. 1989 Aug;5(4):431-40 PMID: 2788443
  15. Role of the carboxy-terminal portion of the HIV-1 transmembrane protein in viral transmission and cytopathogenicity.
    AIDS Res Hum Retroviruses. 1989 Aug;5(4):441-9 PMID: 2788444
  16. The cytoplasmic domain of simian immunodeficiency virus transmembrane protein modulates infectivity.
    J Virol. 1989 Oct;63(10):4395-403 PMID: 2778881
  17. Significance of premature stop codons in env of simian immunodeficiency virus.
    J Virol. 1989 Nov;63(11):4709-14 PMID: 2795718
  18. Formation of an infectious virus-antibody complex with Rous sarcoma virus and antibodies directed against the major virus glycoprotein.
    J Virol. 1976 Mar;17(3):1063-7 PMID: 56458
  19. Specific selection of host cell glycoproteins during assembly of murine leukaemia virus and vesicular stomatitis virus: presence of Thy-1 glycoprotein and absence of H-2, Pgp-1 and T-200 glycoproteins on the envelopes of these virus particles.
    J Gen Virol. 1983 Jun;64 (Pt 6):1241-53 PMID: 6133909
  20. Assembly of xenotropic murine leukaemia virus-related antigens from the surface of mouse L cells by vesicular stomatitis virus.
    Acta Virol. 1983 Mar;27(2):105-9 PMID: 6135328
  21. Altered cytoplasmic domains affect intracellular transport of the vesicular stomatitis virus glycoprotein.
    Cell. 1983 Sep;34(2):513-24 PMID: 6352053
  22. Rous sarcoma virus p19 and gp35 can be chemically crosslinked to high molecular weight complexes. An insight into virus assembly.
    J Mol Biol. 1984 Apr 5;174(2):297-317 PMID: 6325711
  23. Quantitative separation of murine leukemia virus proteins by reversed-phase high-pressure liquid chromatography reveals newly described gag and env cleavage products.
    J Virol. 1984 Nov;52(2):492-500 PMID: 6333515
  24. A deletion mutation in the 5' part of the pol gene of Moloney murine leukemia virus blocks proteolytic processing of the gag and pol polyproteins.
    J Virol. 1985 Mar;53(3):899-907 PMID: 3882995
  25. Murine leukemia virus maturation: protease region required for conversion from "immature" to "mature" core form and for virus infectivity.
    Virology. 1985 Sep;145(2):280-92 PMID: 2411050
  26. Cytoplasmic domains of cellular and viral integral membrane proteins substitute for the cytoplasmic domain of the vesicular stomatitis virus glycoprotein in transport to the plasma membrane.
    J Cell Biol. 1986 Jun;102(6):2147-57 PMID: 3011809
  27. Infectious mutants of HTLV-III with changes in the 3' region and markedly reduced cytopathic effects.
    Science. 1986 Aug 8;233(4764):655-9 PMID: 3014663
  28. SIV adaptation to human cells.
    Nature. 1989 Oct 19;341(6243):573-4 PMID: 2677749
  29. Shortened cytoplasmic domain affects intracellular transport but not nuclear localization of a viral glycoprotein.
    J Biol Chem. 1990 Jan 25;265(3):1777-82 PMID: 2153143
  30. Oligomeric structure of the human immunodeficiency virus type 1 envelope glycoprotein.
    Proc Natl Acad Sci U S A. 1990 Jan;87(2):648-52 PMID: 2300552
  31. The carboxy terminus of human immunodeficiency virus type 1 gp160 limits its proteolytic processing and transport in transfected cell lines.
    J Virol. 1990 Jun;64(6):3100-3 PMID: 2186180
  32. Synthesis and processing of the transmembrane envelope protein of equine infectious anemia virus.
    J Virol. 1990 Aug;64(8):3770-8 PMID: 2164597
  33. Efficient incorporation of human CD4 protein into avian leukosis virus particles.
    Science. 1990 Dec 7;250(4986):1421-3 PMID: 2175047
  34. Common precursor for Rauscher leukemia virus gp69/71, p15(E), and p12(E).
    J Virol. 1977 Sep;23(3):787-98 PMID: 894795
  35. An analysis of type-C retrovirus polypeptides and their associations in the virion.
    Virology. 1978 Jan;84(1):19-31 PMID: 202077
  36. Specific incorporation of host cell surface proteins into budding vesicular stomatitis virus particles.
    Cell. 1980 Jan;19(1):161-9 PMID: 6244101
  37. Murine mammary tumor virus structural protein interactions: formation of oligomeric complexes with cleavable cross-linking agents.
    J Virol. 1980 Sep;35(3):937-48 PMID: 6252348
  38. Comparative immunofluorescence of murine leukemia virus-derived membrane-associated antigens.
    Virology. 1983 Jan 30;124(2):259-73 PMID: 6337447
  39. Oligomers of the cytoplasmic domain of the p62/E2 membrane protein of Semliki Forest virus bind to the nucleocapsid in vitro.
    J Virol. 1990 Oct;64(10):4678-83 PMID: 2398527
  40. Retrovirus envelope glycoproteins.
    Curr Top Microbiol Immunol. 1990;157:187-253 PMID: 2203609
  41. The cytoplasmic tail of HIV-1 gp160 contains regions that associate with cellular membranes.
    Virology. 1991 Jan;180(1):439-41 PMID: 1984664
  42. Biological and immunological properties of human immunodeficiency virus type 1 envelope glycoprotein: analysis of proteins with truncations and deletions expressed by recombinant vaccinia viruses.
    J Virol. 1991 Jan;65(1):31-41 PMID: 1985202
  43. A specific inhibitor of cysteine proteases impairs a Vif-dependent modification of human immunodeficiency virus type 1 Env protein.
    J Virol. 1991 Mar;65(3):1325-31 PMID: 1995946
  44. Human immunodeficiency virus envelope protein determines the site of virus release in polarized epithelial cells.
    Proc Natl Acad Sci U S A. 1991 May 1;88(9):3987-91 PMID: 2023946
  45. Analysis of mutations in the envelope gene of Moloney murine leukemia virus: separation of infectivity from superinfection resistance.
    Virology. 1991 Aug;183(2):545-54 PMID: 1853560
  46. Inhibition of influenza virus formation by a peptide that corresponds to sequences in the cytoplasmic domain of the hemagglutinin.
    Virology. 1991 Aug;183(2):769-72 PMID: 1853575
  47. The cytoplasmic domain of alphavirus E2 glycoprotein contains a short linear recognition signal required for viral budding.
    EMBO J. 1991 Sep;10(9):2343-51 PMID: 1714373
  48. A viral protease-mediated cleavage of the transmembrane glycoprotein of Mason-Pfizer monkey virus can be suppressed by mutations within the matrix protein.
    Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3443-7 PMID: 1565636
  49. Effects of deletions in the cytoplasmic domain on biological functions of human immunodeficiency virus type 1 envelope glycoproteins.
    J Virol. 1992 Jun;66(6):3306-15 PMID: 1583717
  50. Cytoplasmic domain truncation enhances fusion activity by the exterior glycoprotein complex of human immunodeficiency virus type 2 in selected cell types.
    J Virol. 1992 Jun;66(6):3971-5 PMID: 1583738
  51. Retained in vitro infectivity and cytopathogenicity of HIV-1 despite truncation of the C-terminal tail of the env gene product.
    Virology. 1992 Jul;189(1):167-77 PMID: 1604808
  52. The matrix protein of human immunodeficiency virus type 1 is required for incorporation of viral envelope protein into mature virions.
    J Virol. 1992 Aug;66(8):4966-71 PMID: 1629961
  53. Effects of mutations within the 3' orf open reading frame region of human T-cell lymphotropic virus type III (HTLV-III/LAV) on replication and cytopathogenicity.
    J Virol. 1986 Nov;60(2):754-60 PMID: 3490583
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.67.1.213-221.1993
Published
1993-01-00
Pages
213-21
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC237354
Subset
IM
Grants
NCI NIH HHS · CA-39805 · United States
NHLBI NIH HHS · HL-33774 · United States
External Links
PubMed source DOI: 10.1128/JVI.67.1.213-221.1993 PMC Full Text View journal details
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]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2