Home LiteratureArticle Details
PMID: 2164607 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

N myristoylation of the spleen necrosis virus matrix protein is required for correct association of the Gag polyprotein with intracellular membranes and for particle formation.

Journal of virology ·Vol. 64 ·No. 8 ·1990-08-00 ·Pages 3995-4001

Weaver TA, Panganiban AT

Abstract

To determine whether myristoylation is required for spleen necrosis virus replication, we constructed a substitution mutation in the gag gene that alters the putative myristate acceptor glycine residue. This single amino acid change was lethal for virus replication, resulted in aberrant proteolytic processing, and interrupted virion assembly and the release of virus from cells. Immunofluorescence analysis indicated that the amount of Gag polyprotein at the cell periphery and in Golgi-associated vesicles is severely reduced in the myristoylation mutant, indicating that correct intracellular targeting is affected by a lack of myristoylation. Coexpression of wild-type Gag polyprotein did not complement and rescue the replication-defective phenotype of the myristoylation mutant. Thus, it appears that the nonmyristoylated polyproteins are incapable of interacting with their myristoylated counterparts to form biologically active particles.

MeSH Terms
Animals Cell Line Codon/genetics DNA, Viral/genetics Gene Products, gag/genetics,metabolism Genes, gag Intracellular Membranes/metabolism Mutation Myristic Acid Myristic Acids/metabolism Protein Binding Protein Processing, Post-Translational Retroviridae/genetics,metabolism,physiology Transfection Viral Matrix Proteins/genetics,metabolism Virus Replication
Chemicals
Codon DNA, Viral Gene Products, gag Myristic Acids Viral Matrix Proteins Myristic Acid
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Weaver T A
McArdle Laboratory for Cancer Research, University of Wisconsin-Madison 53706.
Panganiban A T
References (53)
53 references, click to expand
  1. In vivo modification of retroviral gag gene-encoded polyproteins by myristic acid.
    J Virol. 1983 May;46(2):355-61 PMID: 6302307
  2. High-efficiency ligation and recombination of DNA fragments by vertebrate cells.
    Science. 1983 May 6;220(4597):606-9 PMID: 6301012
  3. 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
  4. Expression from an internal AUG codon of herpes simplex thymidine kinase gene inserted in a retrovirus vector.
    Mol Cell Biol. 1984 Apr;4(4):743-8 PMID: 6325894
  5. New procedure for DNA transfection with polycation and dimethyl sulfoxide.
    Mol Cell Biol. 1984 Jun;4(6):1172-4 PMID: 6330534
  6. Rapid and efficient site-specific mutagenesis without phenotypic selection.
    Proc Natl Acad Sci U S A. 1985 Jan;82(2):488-92 PMID: 3881765
  7. Specificity of fatty acid acylation of cellular proteins.
    J Biol Chem. 1985 Mar 25;260(6):3784-90 PMID: 3972848
  8. Myristic acid is attached to the transforming protein of Rous sarcoma virus during or immediately after synthesis and is present in both soluble and membrane-bound forms of the protein.
    Mol Cell Biol. 1984 Dec;4(12):2697-704 PMID: 6441887
  9. 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
  10. Fatty acylation of cellular proteins. Temporal and subcellular differences between palmitate and myristate acylation.
    J Biol Chem. 1986 Feb 15;261(5):2458-66 PMID: 3944142
  11. Protein fatty acid acylation: enzymatic synthesis of an N-myristoylglycyl peptide.
    Proc Natl Acad Sci U S A. 1986 May;83(9):2812-6 PMID: 3517877
  12. Analysis of retroviral pol gene products with antisera raised against fusion proteins produced in Escherichia coli.
    J Virol. 1986 Aug;59(2):328-40 PMID: 2426463
  13. A single N-linked oligosaccharide at either of the two normal sites is sufficient for transport of vesicular stomatitis virus G protein to the cell surface.
    Mol Cell Biol. 1985 Nov;5(11):3074-83 PMID: 3018499
  14. Myristylation site in Pr65gag is essential for virus particle formation by Moloney murine leukemia virus.
    Proc Natl Acad Sci U S A. 1986 Oct;83(19):7246-50 PMID: 3489936
  15. High mutation rate of a spleen necrosis virus-based retrovirus vector.
    Mol Cell Biol. 1986 Dec;6(12):4387-95 PMID: 3796606
  16. Fine structure of human immunodeficiency virus (HIV) and immunolocalization of structural proteins.
    Virology. 1987 Jan;156(1):171-6 PMID: 3643678
  17. Myristylation is required for intracellular transport but not for assembly of D-type retrovirus capsids.
    J Virol. 1987 Apr;61(4):1045-53 PMID: 3493352
  18. Myristic acid is coupled to a structural protein of polyoma virus and SV40.
    Nature. 1987 Apr 9-15;326(6113):619-22 PMID: 3031509
  19. Myristylation of picornavirus capsid protein VP4 and its structural significance.
    Nature. 1987 Jun 11-17;327(6122):482-6 PMID: 3035380
  20. An evaluation of confocal versus conventional imaging of biological structures by fluorescence light microscopy.
    J Cell Biol. 1987 Jul;105(1):41-8 PMID: 3112165
  21. Capsid protein VP4 of poliovirus is N-myristoylated.
    Proc Natl Acad Sci U S A. 1987 Nov;84(22):7827-31 PMID: 2825164
  22. Acylation of proteins with myristic acid occurs cotranslationally.
    Science. 1987 Nov 27;238(4831):1275-8 PMID: 3685978
  23. A nucleotide substitution in the gag N terminus of the endogenous ecotropic DBA/2 virus prevents Pr65gag myristylation and virus replication.
    J Virol. 1988 Sep;62(9):3217-23 PMID: 2841473
  24. Heteroatom-substituted fatty acid analogs as substrates for N-myristoyltransferase: an approach for studying both the enzymology and function of protein acylation.
    Proc Natl Acad Sci U S A. 1988 Dec;85(23):8795-9 PMID: 3143109
  25. Processing of the structural proteins of human immunodeficiency virus type 1 in the presence of monensin and cerulenin.
    Proc Natl Acad Sci U S A. 1988 Dec;85(23):9283-6 PMID: 3194424
  26. Fatty acylation of proteins.
    Annu Rev Cell Biol. 1988;4:611-47 PMID: 3058168
  27. Role of reticuloendotheliosis virus envelope glycoprotein in superinfection interference.
    J Virol. 1989 Jan;63(1):273-80 PMID: 2535733
  28. Unmyristylated Moloney murine leukemia virus Pr65gag is excluded from virus assembly and maturation events.
    J Virol. 1989 May;63(5):2370-3 PMID: 2649693
  29. Role of capsid precursor processing and myristoylation in morphogenesis and infectivity of human immunodeficiency virus type 1.
    Proc Natl Acad Sci U S A. 1989 Aug;86(15):5781-5 PMID: 2788277
  30. Creation and expression of myristylated forms of Rous sarcoma virus gag protein in mammalian cells.
    J Virol. 1989 Oct;63(10):4331-43 PMID: 2550669
  31. Assembly and release of HIV-1 precursor Pr55gag virus-like particles from recombinant baculovirus-infected insect cells.
    Cell. 1989 Oct 6;59(1):103-12 PMID: 2676191
  32. Replication of human immunodeficiency virus 1 and Moloney murine leukemia virus is inhibited by different heteroatom-containing analogs of myristic acid.
    Proc Natl Acad Sci U S A. 1989 Nov;86(22):8655-9 PMID: 2813417
  33. Role of myristoylation of poliovirus capsid protein VP4 as determined by site-directed mutagenesis of its N-terminal sequence.
    EMBO J. 1989 Sep;8(9):2661-8 PMID: 2555183
  34. Spleen necrosis virus gag polyprotein is necessary for particle assembly and release but not for proteolytic processing.
    J Virol. 1990 Jun;64(6):2642-52 PMID: 2186174
  35. Comparative morphology of avian and murine leukemia viruses.
    J Natl Cancer Inst. 1971 Dec;47(6):1289-98 PMID: 4330466
  36. RNA tumor viruses. Terminology and ultrastructural aspects of virion morphology and replication.
    J Natl Cancer Inst. 1972 Aug;49(2):323-7 PMID: 5076818
  37. A new group of oncogenic viruses: reticuloendotheliosis, chick syncytial, duck infectious anemia, and spleen necrosis viruses.
    J Natl Cancer Inst. 1973 Aug;51(2):489-99 PMID: 4358134
  38. Dependence of Moloney murine leukemia virus production on cell growth.
    Virology. 1975 Sep;67(1):242-8 PMID: 1172324
  39. Comparative ultrastructural study of four reticuloendothelias viruses.
    J Virol. 1975 Oct;16(4):1027-38 PMID: 170410
  40. 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
  41. Electron microscopy of mammalian type-C RNA viruses: use of conditional lethal mutants in studies on virion maturation and assembly.
    Virology. 1976 Oct 15;74(2):459-69 PMID: 62449
  42. Murine leukemia virus morphogenesis: cleavage of P70 in vitro can be accompanied by a shift from a concentrically coiled internal strand ("immature") to a collapsed ("mature") form of the virus core.
    Proc Natl Acad Sci U S A. 1977 Aug;74(8):3446-50 PMID: 410020
  43. Assembly of type C oncornaviruses: a model.
    Science. 1978 Jan 13;199(4325):183-6 PMID: 202022
  44. Membrane properties of the gag gene-coded p15 protein of mouse type-C RNA tumor viruses.
    J Biol Chem. 1978 Mar 10;253(5):1408-14 PMID: 627545
  45. The relative hydrophobicity of oncornaviral structural proteins.
    Virology. 1978 May 15;86(2):398-412 PMID: 208256
  46. High frequency of aberrant expression of Moloney murine leukemia virus in clonal infections.
    Cell. 1978 Jul;14(3):601-9 PMID: 80281
  47. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications.
    Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4 PMID: 388439
  48. Identification of retrovirus matrix proteins by lipid-protein cross-linking.
    J Mol Biol. 1979 Jul 15;131(4):819-37 PMID: 229234
  49. Spontaneous changes in nucleotide sequence in proviruses of spleen necrosis virus, an avian retrovirus.
    Proc Natl Acad Sci U S A. 1982 Feb;79(4):1230-4 PMID: 6951170
  50. n-Tetradecanoyl is the NH2-terminal blocking group of the catalytic subunit of cyclic AMP-dependent protein kinase from bovine cardiac muscle.
    Proc Natl Acad Sci U S A. 1982 Oct;79(20):6128-31 PMID: 6959104
  51. Identification of the NH2-terminal blocking group of calcineurin B as myristic acid.
    FEBS Lett. 1982 Dec 27;150(2):314-8 PMID: 7160476
  52. Myristyl amino-terminal acylation of murine retrovirus proteins: an unusual post-translational proteins modification.
    Proc Natl Acad Sci U S A. 1983 Jan;80(2):339-43 PMID: 6340098
  53. The terminal nucleotides of retrovirus DNA are required for integration but not virus production.
    Nature. 1983 Nov 10-16;306(5939):155-60 PMID: 6316141
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
Published
1990-08-00
Pages
3995-4001
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC249699
Subset
IM
Grants
NCI NIH HHS · CA22443-10 · 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]