Home LiteratureArticle Details
PMID: 15043007 Published · ppublish English Journal Article Review

Virus entry: molecular mechanisms and biomedical applications.

Nature reviews. Microbiology ·Vol. 2 ·No. 2 ·2004-02-00 ·Pages 109-22

Dimitrov DS

Abstract

Viruses have evolved to enter cells from all three domains of life--Bacteria, Archaea and Eukaryotes. Of more than 3,600 known viruses, hundreds can infect human cells and most of those are associated with disease. To gain access to the cell interior, animal viruses attach to host-cell receptors. Advances in our understanding of how viral entry proteins interact with their host-cell receptors and undergo conformational changes that lead to entry offer unprecedented opportunities for the development of novel therapeutics and vaccines.

MeSH Terms
Animals Antibodies, Viral/immunology Humans Membrane Fusion Protein Conformation Receptors, Virus/chemistry,physiology Viral Vaccines/immunology Viruses/pathogenicity,ultrastructure
Chemicals
Antibodies, Viral Receptors, Virus Viral Vaccines
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Dimitrov Dimiter S
Human Immunovirology and Computational Biology Group, Laboratory of Experimental & Computational Biology, Centre for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland 21702-1201, USA. dimitrov@ncifcrf.gov
References (109)
109 references, click to expand
  1. Local actin polymerization and dynamin recruitment in SV40-induced internalization of caveolae.
    Science. 2002 Apr 19;296(5567):535-9 PMID: 11964480
  2. The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy.
    Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10405-10 PMID: 12136130
  3. Structure of dengue virus: implications for flavivirus organization, maturation, and fusion.
    Cell. 2002 Mar 8;108(5):717-25 PMID: 11893341
  4. A novel coronavirus associated with severe acute respiratory syndrome.
    N Engl J Med. 2003 May 15;348(20):1953-66 PMID: 12690092
  5. Protein design of an HIV-1 entry inhibitor.
    Science. 2001 Feb 2;291(5505):884-8 PMID: 11229405
  6. Neutralization of animal viruses.
    Curr Top Microbiol Immunol. 1993;183:1-149 PMID: 8354080
  7. 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
  8. Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution.
    Nature. 1981 Jan 29;289(5796):366-73 PMID: 7464906
  9. HIV-1 entry into T-cells is not dependent on CD4 and CCR5 localization to sphingolipid-enriched, detergent-resistant, raft membrane domains.
    J Biol Chem. 2003 Jan 31;278(5):3153-61 PMID: 12431990
  10. Direct involvement of HERV-W Env glycoprotein in human trophoblast cell fusion and differentiation.
    Mol Cell Biol. 2003 May;23(10):3566-74 PMID: 12724415
  11. An early stage of membrane fusion mediated by the low pH conformation of influenza hemagglutinin depends upon membrane lipids.
    J Cell Biol. 1997 Jan 13;136(1):81-93 PMID: 9008705
  12. Inhibition of entry of HIV-1 in neural cell lines by antibodies against galactosyl ceramide.
    Science. 1991 Jul 19;253(5017):320-3 PMID: 1857969
  13. Placental endogenous retrovirus (ERV): structural, functional, and evolutionary significance.
    Bioessays. 1998 Apr;20(4):307-16 PMID: 9619102
  14. Spread of HTLV-I between lymphocytes by virus-induced polarization of the cytoskeleton.
    Science. 2003 Mar 14;299(5613):1713-6 PMID: 12589003
  15. Modulation of entry of enveloped viruses by cholesterol and sphingolipids (Review).
    Mol Membr Biol. 2003 Jul-Sep;20(3):243-54 PMID: 12893532
  16. Development of a humanized monoclonal antibody (MEDI-493) with potent in vitro and in vivo activity against respiratory syncytial virus.
    J Infect Dis. 1997 Nov;176(5):1215-24 PMID: 9359721
  17. Structural analysis of the mechanism of adenovirus binding to its human cellular receptor, CAR.
    Science. 1999 Nov 19;286(5444):1579-83 PMID: 10567268
  18. Involvement of lipids in different steps of the flavivirus fusion mechanism.
    J Virol. 2003 Jul;77(14):7856-62 PMID: 12829825
  19. HIV-1 envelope proteins complete their folding into six-helix bundles immediately after fusion pore formation.
    Mol Biol Cell. 2003 Mar;14(3):926-38 PMID: 12631714
  20. HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites.
    Nature. 2002 Dec 12;420(6916):678-82 PMID: 12478295
  21. Investigation of pathways for the low-pH conformational transition in influenza hemagglutinin.
    Biophys J. 2003 Mar;84(3):1926-39 PMID: 12609895
  22. Antibody interactions with rhinovirus: lessons for mechanisms of neutralization and the role of immunity in viral evolution.
    Curr Top Microbiol Immunol. 2001;260:1-28 PMID: 11443870
  23. Structure of a human common cold virus and functional relationship to other picornaviruses.
    Nature. 1985 Sep 12-18;317(6033):145-53 PMID: 2993920
  24. Antibodies, viruses and vaccines.
    Nat Rev Immunol. 2002 Sep;2(9):706-13 PMID: 12209139
  25. Human erythrocyte glycosphingolipids as alternative cofactors for human immunodeficiency virus type 1 (HIV-1) entry: evidence for CD4-induced interactions between HIV-1 gp120 and reconstituted membrane microdomains of glycosphingolipids (Gb3 and GM3).
    J Virol. 1999 Jun;73(6):5244-8 PMID: 10233996
  26. Broadly cross-reactive HIV-1-neutralizing human monoclonal Fab selected for binding to gp120-CD4-CCR5 complexes.
    Proc Natl Acad Sci U S A. 2002 May 14;99(10):6913-8 PMID: 11997472
  27. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus.
    Nature. 2003 Nov 27;426(6965):450-4 PMID: 14647384
  28. Discovery of a potent small molecule IL-2 inhibitor through fragment assembly.
    J Am Chem Soc. 2003 Apr 2;125(13):3714-5 PMID: 12656598
  29. Membrane rearrangements in fusion mediated by viral proteins.
    Trends Microbiol. 1997 Sep;5(9):349-55 PMID: 9294890
  30. Nanoparticles for the delivery of genes and drugs to human hepatocytes.
    Nat Biotechnol. 2003 Aug;21(8):885-90 PMID: 12833071
  31. Progress and problems with the use of viral vectors for gene therapy.
    Nat Rev Genet. 2003 May;4(5):346-58 PMID: 12728277
  32. Alpharetrovirus envelope-receptor interactions.
    Curr Top Microbiol Immunol. 2003;281:107-36 PMID: 12932076
  33. Control of baculovirus gp64-induced syncytium formation by membrane lipid composition.
    J Virol. 1995 May;69(5):3049-58 PMID: 7707532
  34. The SARS-CoV S glycoprotein: expression and functional characterization.
    Biochem Biophys Res Commun. 2003 Dec 26;312(4):1159-64 PMID: 14651994
  35. Observation of single influenza virus-cell fusion and measurement by fluorescence video microscopy.
    Proc Natl Acad Sci U S A. 1990 Mar;87(5):1850-4 PMID: 2308945
  36. Neutralizing antibody to human rhinovirus 14 penetrates the receptor-binding canyon.
    Nature. 1996 Sep 26;383(6598):350-4 PMID: 8848050
  37. Gating kinetics of pH-activated membrane fusion of vesicular stomatitis virus with cells: stopped-flow measurements by dequenching of octadecylrhodamine fluorescence.
    Biochemistry. 1990 Feb 6;29(5):1303-8 PMID: 2157487
  38. Crystal structure of reovirus attachment protein sigma1 reveals evolutionary relationship to adenovirus fiber.
    EMBO J. 2002 Jan 15;21(1-2):1-11 PMID: 11782420
  39. Secretory and viral fusion may share mechanistic events with fusion between curved lipid bilayers.
    Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9274-9 PMID: 9689070
  40. Conformational changes and fusion activity of vesicular stomatitis virus glycoprotein: [125I]iodonaphthyl azide photolabeling studies in biological membranes.
    Biochemistry. 1997 Jul 22;36(29):8890-6 PMID: 9220976
  41. Development and use of palivizumab (Synagis): a passive immunoprophylactic agent for RSV.
    J Infect Chemother. 2002 Sep;8(3):201-6 PMID: 12373481
  42. Cytolysis by CCR5-using human immunodeficiency virus type 1 envelope glycoproteins is dependent on membrane fusion and can be inhibited by high levels of CD4 expression.
    J Virol. 2003 Jun;77(12):6645-59 PMID: 12767984
  43. Anthrax X-rayed: new opportunities for biodefence.
    Trends Pharmacol Sci. 2002 Dec;23(12):539-41 PMID: 12457764
  44. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody.
    Nature. 1998 Jun 18;393(6686):648-59 PMID: 9641677
  45. A spring-loaded mechanism for the conformational change of influenza hemagglutinin.
    Cell. 1993 May 21;73(4):823-32 PMID: 8500173
  46. Influenza hemagglutinin is spring-loaded by a metastable native conformation.
    Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14306-13 PMID: 9405608
  47. Discovering high-affinity ligands for proteins: SAR by NMR.
    Science. 1996 Nov 29;274(5292):1531-4 PMID: 8929414
  48. Distinct cellular receptor interactions in poliovirus and rhinoviruses.
    EMBO J. 2000 Mar 15;19(6):1207-16 PMID: 10716921
  49. Poliovirus cell entry: common structural themes in viral cell entry pathways.
    Annu Rev Microbiol. 2002;56:677-702 PMID: 12142481
  50. In vitro selection of viral vectors with modified tropism: the adeno-associated virus display.
    Mol Ther. 2003 Jul;8(1):151-7 PMID: 12842438
  51. Cell biology of virus entry.
    Cell. 2000 Jun 23;101(7):697-702 PMID: 10892741
  52. Virus versus antibody.
    Structure. 1997 May 15;5(5):591-3 PMID: 9235220
  53. Evolution of cell recognition by viruses.
    Science. 2001 May 11;292(5519):1102-5 PMID: 11352064
  54. A ligand-binding pocket in the dengue virus envelope glycoprotein.
    Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):6986-91 PMID: 12759475
  55. Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid.
    Nature. 1988 Jun 2;333(6172):426-31 PMID: 3374584
  56. Acid-induced changes in thermal stability and fusion activity of influenza hemagglutinin.
    Biochemistry. 2002 Feb 12;41(6):2044-54 PMID: 11827552
  57. Epstein-Barr virus receptor of human B lymphocytes is the C3d receptor CR2.
    Proc Natl Acad Sci U S A. 1984 Jul;81(14):4510-4 PMID: 6087328
  58. Kinetics of HIV-1 interactions with sCD4 and CD4+ cells: implications for inhibition of virus infection and initial steps of virus entry into cells.
    Virology. 1992 Apr;187(2):398-406 PMID: 1347667
  59. Novel therapies based on mechanisms of HIV-1 cell entry.
    N Engl J Med. 2003 May 29;348(22):2228-38 PMID: 12773651
  60. Binding of small molecules to an adaptive protein-protein interface.
    Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1603-8 PMID: 12582206
  61. Fusion of Semliki forest virus with the plasma membrane can be induced by low pH.
    J Cell Biol. 1980 Oct;87(1):264-72 PMID: 7419594
  62. Three-dimensional structure of poliovirus at 2.9 A resolution.
    Science. 1985 Sep 27;229(4720):1358-65 PMID: 2994218
  63. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor.
    Science. 1996 May 10;272(5263):872-7 PMID: 8629022
  64. Dissecting virus entry via endocytosis.
    J Gen Virol. 2002 Jul;83(Pt 7):1535-1545 PMID: 12075072
  65. Membrane fusion.
    Chem Rev. 2003 Jan;103(1):53-69 PMID: 12517181
  66. Real-time single-molecule imaging of the infection pathway of an adeno-associated virus.
    Science. 2001 Nov 30;294(5548):1929-32 PMID: 11729319
  67. Specific roles for lipids in virus fusion and exit. Examples from the alphaviruses.
    Subcell Biochem. 2000;34:409-55 PMID: 10808340
  68. Pleconaril, a novel antipicornaviral agent.
    Pharmacotherapy. 2003 Mar;23(3):339-48 PMID: 12627933
  69. Molecular breeding of viruses.
    Nat Genet. 2000 Aug;25(4):436-9 PMID: 10932190
  70. Antibody neutralization and escape by HIV-1.
    Nature. 2003 Mar 20;422(6929):307-12 PMID: 12646921
  71. Visualizing infection of individual influenza viruses.
    Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9280-5 PMID: 12883000
  72. Quantitation of human immunodeficiency virus type 1 infection kinetics.
    J Virol. 1993 Apr;67(4):2182-90 PMID: 8445728
  73. Entry of viruses through the epithelial barrier: pathogenic trickery.
    Nat Rev Mol Cell Biol. 2003 Jan;4(1):57-68 PMID: 12511869
  74. A direct comparison of the activities of two humanized respiratory syncytial virus monoclonal antibodies: MEDI-493 and RSHZl9.
    J Infect Dis. 1999 Jul;180(1):35-40 PMID: 10353858
  75. Cryo-electron microscopy reveals the functional organization of an enveloped virus, Semliki Forest virus.
    Mol Cell. 2000 Feb;5(2):255-66 PMID: 10882067
  76. Epidermal growth factor receptor is a cellular receptor for human cytomegalovirus.
    Nature. 2003 Jul 24;424(6947):456-61 PMID: 12879076
  77. Reversible stages of the low-pH-triggered conformational change in influenza virus hemagglutinin.
    EMBO J. 2002 Nov 1;21(21):5701-10 PMID: 12411488
  78. Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin.
    Annu Rev Biochem. 2000;69:531-69 PMID: 10966468
  79. Entry of alphaherpesviruses mediated by poliovirus receptor-related protein 1 and poliovirus receptor.
    Science. 1998 Jun 5;280(5369):1618-20 PMID: 9616127
  80. The structural biology of type I viral membrane fusion.
    Nat Rev Mol Cell Biol. 2003 Apr;4(4):309-19 PMID: 12671653
  81. Structure of a murine leukemia virus receptor-binding glycoprotein at 2.0 angstrom resolution.
    Science. 1997 Sep 12;277(5332):1662-6 PMID: 9287219
  82. Structural characterization of respiratory syncytial virus fusion inhibitor escape mutants: homology model of the F protein and a syncytium formation assay.
    Virology. 2003 Jul 5;311(2):275-88 PMID: 12842618
  83. Tyrosine sulfation of human antibodies contributes to recognition of the CCR5 binding region of HIV-1 gp120.
    Cell. 2003 Jul 25;114(2):161-70 PMID: 12887918
  84. Antibodies for the prevention and treatment of viral diseases.
    Antiviral Res. 2000 Aug;47(2):57-77 PMID: 10996394
  85. Herpes simplex virus glycoprotein D bound to the human receptor HveA.
    Mol Cell. 2001 Jul;8(1):169-79 PMID: 11511370
  86. New anti-HIV agents and targets.
    Med Res Rev. 2002 Nov;22(6):531-65 PMID: 12369088
  87. Structural evidence for common functions and ancestry of the reovirus and adenovirus attachment proteins.
    Rev Med Virol. 2003 Mar-Apr;13(2):123-32 PMID: 12627395
  88. Molecular tectonic model of virus structural transitions: the putative cell entry states of poliovirus.
    J Virol. 2000 Feb;74(3):1342-54 PMID: 10627545
  89. Targeted gene delivery by virosomes.
    Methods Mol Biol. 2002;199:163-73 PMID: 12094567
  90. The HIV Env-mediated fusion reaction.
    Biochim Biophys Acta. 2003 Jul 11;1614(1):36-50 PMID: 12873764
  91. The Fusion glycoprotein shell of Semliki Forest virus: an icosahedral assembly primed for fusogenic activation at endosomal pH.
    Cell. 2001 Apr 6;105(1):137-48 PMID: 11301009
  92. The avian retrovirus avian sarcoma/leukosis virus subtype A reaches the lipid mixing stage of fusion at neutral pH.
    J Virol. 2003 Mar;77(5):3058-66 PMID: 12584331
  93. 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
  94. Mechanisms of viral membrane fusion and its inhibition.
    Annu Rev Biochem. 2001;70:777-810 PMID: 11395423
  95. Biological function of the low-pH, fusion-inactive conformation of rabies virus glycoprotein (G): G is transported in a fusion-inactive state-like conformation.
    J Virol. 1995 Sep;69(9):5528-34 PMID: 7543584
  96. Cell fusion: a hidden enemy?
    Cancer Cell. 2003 May;3(5):445-8 PMID: 12781362
  97. The structure of the fusion glycoprotein of Newcastle disease virus suggests a novel paradigm for the molecular mechanism of membrane fusion.
    Structure. 2001 Mar 7;9(3):255-66 PMID: 11286892
  98. Sphingolipid and cholesterol dependence of alphavirus membrane fusion. Lack of correlation with lipid raft formation in target liposomes.
    J Biol Chem. 2002 Oct 11;277(41):38141-7 PMID: 12138173
  99. The coronavirus spike protein is a class I virus fusion protein: structural and functional characterization of the fusion core complex.
    J Virol. 2003 Aug;77(16):8801-11 PMID: 12885899
  100. The envelope glycoprotein from tick-borne encephalitis virus at 2 A resolution.
    Nature. 1995 May 25;375(6529):291-8 PMID: 7753193
  101. Characterization of the equilibrium between the native and fusion-inactive conformation of rabies virus glycoprotein indicates that the fusion complex is made of several trimers.
    Virology. 2002 May 25;297(1):128-35 PMID: 12083843
  102. New insights into the spring-loaded conformational change of influenza virus hemagglutinin.
    J Virol. 2002 May;76(9):4456-66 PMID: 11932412
  103. Reversibility in fusion protein conformational changes. The intriguing case of rhabdovirus-induced membrane fusion.
    Subcell Biochem. 2000;34:379-408 PMID: 10808339
  104. The machinery for flavivirus fusion with host cell membranes.
    Curr Opin Microbiol. 2001 Aug;4(4):450-5 PMID: 11495810
  105. Influenza virus hemagglutinin concentrates in lipid raft microdomains for efficient viral fusion.
    Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14610-7 PMID: 14561897
  106. Protein recognition by cell surface receptors: physiological receptors versus virus interactions.
    Trends Biochem Sci. 2002 Mar;27(3):122-6 PMID: 11893508
  107. Retroviral entry mediated by receptor priming and low pH triggering of an envelope glycoprotein.
    Cell. 2000 Nov 10;103(4):679-89 PMID: 11106737
  108. A small molecule HIV-1 inhibitor that targets the HIV-1 envelope and inhibits CD4 receptor binding.
    Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):11013-8 PMID: 12930892
  109. SNARE-mediated membrane fusion.
    Nat Rev Mol Cell Biol. 2001 Feb;2(2):98-106 PMID: 11252968
Article Info
Journal
Nature reviews. Microbiology
Abbr.
Nat Rev Microbiol
ISSN
1740-1526
DOI
10.1038/nrmicro817
Email
dimitrov@ncifcrf.gov
Published
2004-02-00
Pages
109-22
Language
English
Region
England
NLM ID
101190261
PMCID
PMC7097642
Subset
IM
External Links
PubMed source DOI: 10.1038/nrmicro817 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: product@genelibs.com

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