Skip to main content

Viral (HIV) Entry: How Does It Work?

  • Chapter
Entry Inhibitoren

Abstract

HIV life (replication) cycle involves attachment and fusion of the HIV particle with host target cells to initiate the infectious cycle. Entry into the host cell results in conversion of the viral genes from an RNA form to a DNA form and integration of the viral genetic material into the chromosomes of the now infected cell, where it persists for the life of the host cell, resulting in replication and budding forming new virions that are released from the infected host cells.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 6.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Alkhatib G, Combadiere C, Broder CC, et al. CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science 1996, 272:1955–1958

    Article  PubMed  CAS  Google Scholar 

  • Barre-Sinoussi F, Chermann JC, Rey F, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 1983, 220:868–871

    Article  PubMed  CAS  Google Scholar 

  • Benkirane M, Jin DY, Chun RF, et al. Mechanism of transdominant inhibition of CCR5-mediated HIV-1 infection by CCR5 delta 32. J Biol Chem 1997, 272:30603–30606

    Article  PubMed  CAS  Google Scholar 

  • Berger E, Doms R, Fenyö E, et al. A new classification for HIV-1. Nature 1998, 391:240

    Article  PubMed  CAS  Google Scholar 

  • Bozzette S, McCutchan J, Spector S, Wright B, Richman D. A cross-sectional comparison of persons with syncytium-and non-syncytium-inducing HIV. J Infect Dis 1993, 168:1374–1379

    PubMed  CAS  Google Scholar 

  • Brenchley J, Schacker T, Ruff L, et al. CD4R T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med 2004, 200:749–759

    Article  PubMed  CAS  Google Scholar 

  • Carr CM, Kim PS. A spring-loaded mechanism for the conformational change of influenza hemagglutinin. Cell 1993, 73:823–832

    Article  PubMed  CAS  Google Scholar 

  • Chan D, Kim P. HIV entry and its inhibition. Cell 1998, 93:681–684

    Article  PubMed  CAS  Google Scholar 

  • Chan DC, Fass D, Berger JM, et al. Core structure of gp41 from the HIVenvelope glycoprotein Cell 1997, 89:263–273

    CAS  Google Scholar 

  • Connor R, Sheridan K, Ceradini D, Choe S, Landay N. Change in coreceptor use coreceptor use correlates with disease progression in HIV-1-infected individuals. J Exp Med 1997;185:621–628

    Article  PubMed  CAS  Google Scholar 

  • Cormier EG, Dragic T. The crown and stem of the V3 loop play distinct roles in human immunodeficiency virus type 1 envelope glycoprotein interactions with the CCR5 coreceptor. J Virol 2002, 76:8953–8957

    Article  PubMed  CAS  Google Scholar 

  • de Roda Husman AM, Blaak H, Brouwer M, et al. CC chemokine receptor 5 cell-surface expression in relation to CC chemokine receptor 5 genotype and the clinical course of HIV-1 infection. J Immunol 1999, 163:4597–4603

    PubMed  Google Scholar 

  • Dean M, Carrington M, Winkler C, et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Science 1996, 273:1856–1862

    Article  PubMed  CAS  Google Scholar 

  • Deng H, Liu R, Ellmeier W, et al. Identification of a major co-receptor for primary isolates of HIV-1. Nature 1996, 381:661–666

    Article  PubMed  CAS  Google Scholar 

  • Douek D. Disrupting T-cell homeostasis: how HIV-1 infection causes disease. AIDS Rev 2003, 21:172–177

    Google Scholar 

  • Dragic T, Litwin V, Allaway G, et al. HIV-1 entry into CD4R cells is mediated by the chemokine receptor CC-CKR-5. Nature 1996, 381:667–673

    Article  PubMed  CAS  Google Scholar 

  • Dragic T, Trkola A, Lin SW, et al. Amino-terminal substitutions in the CCR5 coreceptor impair gp120 binding and human immunodeficiency virus type 1 entry. J Virol 1998, 72:279–285

    PubMed  CAS  Google Scholar 

  • Dragic T. An overview of the determinants of CCR5 and CXCR4 co-receptor function. J Gen Virol 2001, 82:1807–1814

    PubMed  CAS  Google Scholar 

  • Edwards T, McManus C, Richardson T, et al. Multimeric CD4+ and coreceptor binding is required to activate HIV-1 envelope protein trimers. Program and abstracts of the 8th Conference on Retroviruses and Opportunistic Infections; February 4–8, 2001; Chicago, Illinois. Abstract 105

    Google Scholar 

  • Fass D, Harrison SC, Kim PS. Nat Struct Biol 1996, 3:465–469

    Article  PubMed  CAS  Google Scholar 

  • Feng Y, Broder C, Kennedy P, Berger E. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane. G protein-coupled receptor. Science 1996, 272:872–877

    Article  PubMed  CAS  Google Scholar 

  • Frank I, Pope M. The enigma of dendritic cell-HIV interplay. Curr Mol Med 2002, 2:229–248

    Article  PubMed  CAS  Google Scholar 

  • Furuta RA, Wild CT, Weng Y, et al. Capture of an early fusion-active conformation of HIV-1 gp41. Nat Struct Biol 1998, 5:276–279

    Article  PubMed  CAS  Google Scholar 

  • Gallaher WR, Ball JM, Garry RF, et al. A general model for the transmembrane proteins of HIV and other retroviruses. AIDS Res Hum Retrovir 1989, 5:431–440

    Article  PubMed  CAS  Google Scholar 

  • Gallaher WR. Detection of a fusion peptide sequence in the transmembrane protein of human immunodeficiency virus. Cell 1987, 50:327–328

    Article  PubMed  CAS  Google Scholar 

  • Gupta P, Collins K, Ratner D, et al. Memory CD4R T cells are the earliest detectable HIV-1-infected cells in the female genital mucosal tissue during HIV-1 transmission in an organ culture system. J Virol 2002, 76:9868–9876

    Article  PubMed  CAS  Google Scholar 

  • Harrison SC. Mechanism of membrane fusion by viral envelope proteins. Adv Virus Res 2005, 64:231–261.

    Article  PubMed  CAS  Google Scholar 

  • Hart TK, Kirsh R, Ellens H, et al. Binding of soluble CD4 proteins to human immunodeficiency virus type 1 and infected cells induces release of envelope glycoprotein gp120. Proc Natl Acad Sci USA 1991, 88:2189–2193

    Article  PubMed  CAS  Google Scholar 

  • Hartley O, Klasse PJ, Sattentau QJ, et al. V3: HIV’s switch-hitter. AIDS Res Hum Retrovir 2005, 21:171–189

    Article  PubMed  CAS  Google Scholar 

  • Huang Y, Paxton W, Wolinsky S et al. The role of a mutant CCR5 allele in HIVtransmission and disease progression. Nat Med 1996, 2:1240–1243

    Article  PubMed  CAS  Google Scholar 

  • Jenkis M, Khoruts A, Ingulli E, et al. In vivo activation of antigen-specific CD4 T cells. Annu Rev Immunol 2001, 19:23–45

    Article  Google Scholar 

  • Kawamura T, Kurtz S, Blauvelt A, Shimada S. The role of Langerhans cells in the sexual transmission of HIV. J Dermatol Sci 2005;40:147–155

    Article  PubMed  CAS  Google Scholar 

  • Klatzmann D, Champagne E, Chamaret S, et al. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature 1984, 312:767–768

    Article  PubMed  CAS  Google Scholar 

  • Koot M, Keet I, Vos A, de Goede R, Roos M, Coutinho R. Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD4R cell depletion and progression to AIDS. Ann Intern Med 1993, 118:681–688

    PubMed  CAS  Google Scholar 

  • Kowalski M, Potz J, Basiripour L, et al. Functional regions of the envelope glycoprotein of human immunodeficiency virus type 1. Science 1987;237:1351–1355

    Article  PubMed  CAS  Google Scholar 

  • Kwong PD, Wyatt R, Robinson J, et al. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 1998, 393:648–659

    Article  PubMed  CAS  Google Scholar 

  • Lederman M, Veazey R, Oxfford R, et al. Prevention of vaginal SHIV transmission in rhesus macaques through inhibition of CCR5. Science 2004, 306:485–487

    Article  PubMed  CAS  Google Scholar 

  • Lee B, Leslie G, Soilleux E, et al. Expression of DC-SIGN allows for more efficient entry of human and simian immunodeficiency viruses via CD4 and a coreceptor. J Virol 2001, 75:12028–12038

    Article  PubMed  CAS  Google Scholar 

  • Liu R, Paxton W, Choe S, et al. Homozygous defect in HIV-1 coreceptor accounts for resistance of some mutiplyexposed individuals to HIV-1 infection Cell 1996, 86:367–377

    CAS  Google Scholar 

  • Marmor M, Sheppard HW, Donnell D, et al. Homozygous and heterozygous CCR5-Delta32genotypes are associated with resistance to HIV infection. J Acquir Immune Defic Syndr 2001, 27:472–481

    PubMed  CAS  Google Scholar 

  • Mehandru S, Poles M, Tenner-Racz K, et al. Primary HIV-1 infection is associated with preferential depletion of CD4R T lymphocytes from effector sites in the gastrointestinal tract. J Exp Med 2004, 200:761–770

    Article  PubMed  CAS  Google Scholar 

  • Moore J, Kitchen S, Pugach P, Zack J. The CCR5 and CXCR4 coreceptors-central to understanding the transmission and pathogenesis of HIV type 1 infection. AIDS Res Hum Retroviruses 2004, 20:111–126

    Article  PubMed  CAS  Google Scholar 

  • Moore JP, McKeating JA, Weiss RA, et al. Dissociation of gp120 from HIV-1 virions induced by soluble CD4. Science 1990, 250:1139–1142

    Article  PubMed  CAS  Google Scholar 

  • Moyle GJ, Wildfire A, Mandalia S, et al. Epidemiology and predictive factors for chemokine receptor use in HIV-1 infection. J Inf Dis 2005, 191:866–872

    Article  Google Scholar 

  • Murphy P, Baggiolini M, Charo I, et al. International union of pharmacology. XXII Nomenclature for chemokine receptors. Pharmacol Rev 2000, 52:145–176

    PubMed  CAS  Google Scholar 

  • Myszka DG, Sweet RW, Hensley P, et al. Energetics of the HIV gp120-CD4 binding reaction. Proc Natl Acad Sci USA 2000, 97:9026–9031

    Article  PubMed  CAS  Google Scholar 

  • Pope M, Betjes M, Romani N, et al. Conjugates of dendritic cells and memory T lymphocytes from skin facilitate productive infection with HIV-1. Cell 1994, 78:389–398

    Article  PubMed  CAS  Google Scholar 

  • Pope M, Gezelter S, Gallo N, Hoffman L, Steinman R. Low levels of HIV-1 infection in cutaneous dendritic cells promote extensive viral replication upon binding to memory CD4R T cells. J Exp Med 1995, 182:2045–2056

    Article  PubMed  CAS  Google Scholar 

  • Pope M, Haase A. Transmission, acute HIV-1 infection and the quest for strategies to prevent infection. Nat Med 2003, 9:847–852

    Article  PubMed  CAS  Google Scholar 

  • Popovic M, Sarin PS, Robert-Gurroff M, et al. Isolation and transmission of human retrovirus (human t-cell leukemia virus). Science 1983;219:856–859

    Article  PubMed  CAS  Google Scholar 

  • Rizzuto CD, Wyatt R, Hernandez-Ramos N, et al. A conserved HIV gp120 glycoprotein structure involved in chemokine receptor binding. Science 1998, 280:1949–1953

    Article  PubMed  CAS  Google Scholar 

  • Samson M, Libert F, Doranz BJ, et al. Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR5 chemokine receptor gene Nature 1996, 382:722–725

    CAS  Google Scholar 

  • Sattentau QJ, Clapham PR, Weiss RA, et al. The human and simian immunodeficiency viruses HIV-1, HIV-2 and SIV interact with similar epitopes on their cellular receptor, the CD4 molecule. AIDS 1988, 2:101–105

    Article  PubMed  CAS  Google Scholar 

  • Sattentau QJ, Moore JP. Conformational changes induced in the human immunodeficiency virus envelope glycoprotein by soluble CD4 binding. J Exp Med 1991, 174:407–415

    Article  PubMed  CAS  Google Scholar 

  • Schuitemaker H, Koot M, Kootstra N, et al. Biological phenotype of HIV type 1 clones at different stages of infection: progression of disease is associated with a shift from monocytotropic to T-cell-tropic virus populations. J Virol 1992, 66:1354–1360

    PubMed  CAS  Google Scholar 

  • Spijderman I, de Wolf F, Langendam M, Schuitemaker H, Coutinho R. Emergence of syncytium-inducing HIV type 1 variants coincides with a progression to AIDS. J Infect Dis 1998, 178:397–403

    Google Scholar 

  • Spira A, Marx P, Patterson B, et al. Cellular targets of infection and route of viral dissemination after an intravaginal inoculation of simian immunodeficiency virus into rhesus macaques. J Exp Med 1996, 183:215–225

    Article  PubMed  CAS  Google Scholar 

  • Tersmette M, de Goede R, Al B, et al. Differential syncytium-inducing capacity of HIV isolates: frequent detection of syncytium-inducing isolates in patients with AIDS and AIDS-related complex. J Virol 1988, 62:2026–2032

    PubMed  CAS  Google Scholar 

  • Veaze R, DeMaria M, Chalifoux L, et al. Gastrointestinal tract as a major site of CD4R T cell depletion and viral replication in SIV infection. Science 1998, 280:427–431

    Article  Google Scholar 

  • Weiss RA, Clapham PR, McClure MO, et al. Human immunodeficiency viruses: neutralization and receptors. J Acquir Immune Defic Syndr 1988, 1:536–541

    PubMed  CAS  Google Scholar 

  • Weissenhorn W, Dessen A, Harrison SC, et al. Atomic structure of the ectodomain from HIV-1 gp41. Nature 1997, 387:426–430

    Article  PubMed  CAS  Google Scholar 

  • Weissenhorn W, Carfi A, Lee KH, et al. Mol Cell 1998, 2:605–616

    Article  PubMed  CAS  Google Scholar 

  • Wessenhorn W, Calder LJ, Dessen A, Laue T, Skehel JJ, Wiley DC. Assembly of a rod-shaped chimera of a trimeric GCN4 zipper and the HIV gp41 ectodomain expressed in Escherichia coli. Proc Natl Acad Sci USA 1997, 94:6065–6069

    Article  Google Scholar 

  • Wu L, Paxton WA, Kassam N, et al. CCR5 levels and expression pattern correlate with infectability by macrophagetropic HIV-1, in vitro. J Exp Med 1997, 185:1681–1691

    Article  PubMed  CAS  Google Scholar 

  • Wu L, Paxton WA, Kassam N, et al. Interaction of chemokine receptor CCR5 with its ligands: multiple domains for HIV-1 gp120 binding and a single domain for chemokine binding. J Exp Med 1997, 186:1373–1381

    Article  PubMed  CAS  Google Scholar 

  • Wyatt R, Sodroski J. The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens». Science 1998, 280:1884–1888

    Article  PubMed  CAS  Google Scholar 

  • Yachou A, Sekaly RP. Binding of soluble recombinant HIV envelope glycoprotein, rgp120, induces conformational changes in the cellular membrane-anchored CD4 molecule. Biochem Biophys Res Commun 1999, 265:428–433

    Article  PubMed  CAS  Google Scholar 

  • Zhang L, He T, Talal A, Wang G, Frankel S, Ho D. In vivo distribution of the HIV/simian immunodeficiency virus coreceptors: CXCR4, CCR5, and CCR5. J Virol 1998, 72:5035–5045

    PubMed  CAS  Google Scholar 

  • Zhang Z, Schuler T, Zupancic M, et al. Sexual transmission and propagation of simian and HIV in two distinguishable populations of CD4R T cells. Science 1999, 286:1353–1357

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer Medizin Verlag Heidelberg

About this chapter

Cite this chapter

Panos, G., Nelson, M. (2008). Viral (HIV) Entry: How Does It Work?. In: Jäger, H. (eds) Entry Inhibitoren. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-78358-9_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-78358-9_1

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-78357-2

  • Online ISBN: 978-3-540-78358-9

  • eBook Packages: Medicine (German Language)

Publish with us

Policies and ethics