Encyclopedia of AIDS

Living Edition
| Editors: Thomas J. Hope, Douglas Richman, Mario Stevenson

Tropism and Properties of the HIV-1 Envelope Glycoprotein in Transmission

  • Paul Clapham
  • Mohan Somasundaran
  • Katherine Luzuriaga
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-9610-6_149-1

Definition

The envelope glycoprotein (Env) spikes on transmitting HIV-1 virus particles mediate infection of the first cells in the new host. These Envs must elude host defenses including innate inhibitors and sometimes neutralizing antibodies. They may also direct mechanisms to penetrate epithelial cell barriers to facilitate mucosal transmission.

Prophylactic vaccines that elicit neutralizing antibodies and microbicides need to be designed and optimized to target transmitting viruses. However, it is as yet unclear whether Envs of viruses that successfully transmit carry specific properties or vulnerabilities that can be targeted by such strategies. What we do know is that viruses that use the coreceptor, CCR5, are preferentially transmitted and that early data suggest these viruses primarily infect CD4+ T-cells over macrophages or dendritic cells.

Some transmitted viruses carry Envs with fewer surface sugars and shorter variable loops that usually protect against neutralizing...

Keywords

Sugar Permeability Carbohydrate Lipase Heparin 
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Notes

Acknowledgments

The authors wish to acknowledge NIH R01 grants AI089334 and AI097265 that support their research in this area.

References

  1. Agace WW, Amara A, Roberts AI, Pablos JL, Thelen M, Uguccioni M, Li XY, Marsal J, Arenzana-Seisdedos F, Delauney T, Ebert EC, Moser B, Parker CM. Constitutive expression of stromal derived factor-1 by mucosal epithelia and its role in HIV transmission and propagation. Curr Biol. 2000;10:325–8.PubMedCrossRefGoogle Scholar
  2. Arthos J, Cicala C, Martinelli E, Macleod K, Van Ryk D, Wei D, Xiao Z, Veenstra TD, Conrad TP, Lempicki RA, McLaughlin S, Pascuccio M, Gopaul R, McNally J, Cruz CC, Censoplano N, Chung E, Reitano KN, Kottilil S, Goode DJ, Fauci AS. HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells. Nat Immunol. 2008;9:301–9.PubMedCrossRefGoogle Scholar
  3. Chen P, Hubner W, Spinelli MA, Chen BK. Predominant mode of human immunodeficiency virus transfer between T cells is mediated by sustained Env-dependent neutralization-resistant virological synapses. J Virol. 2007;81:12582–95.PubMedCrossRefPubMedCentralGoogle Scholar
  4. Chohan BH, Piantadosi A, Overbaugh J. HIV-1 superinfection and its implications for vaccine design. Curr HIV Res. 2010;8:596–601.PubMedCrossRefGoogle Scholar
  5. Clapham PR, McKnight A. Cell surface receptors, virus entry and tropism of primate lentiviruses. J Gen Virol. 2002;83:1809–29.PubMedGoogle Scholar
  6. Duenas-Decamp MJ, Peters PJ, Repik A, Musich T, Gonzalez-Perez MP, Caron C, Brown R, Ball J, Clapham PR. Variation in the biological properties of HIV-1 R5 envelopes: implications of envelope structure, transmission and pathogenesis. Future Virol. 2010;5:417–33.CrossRefGoogle Scholar
  7. Fouda GG, Yates NL, Pollara J, Shen X, Overman GR, Mahlokozera T, Wilks AB, Kang HH, Salazar-Gonzalez JF, Salazar MG, Kalilani L, Meshnick SR, Hahn BH, Shaw GM, Lovingood RV, Denny TN, Haynes B, Letvin NL, Ferrari G, Montefiori DC, Tomaras GD, Permar SR. HIV-specific functional antibody responses in breast milk mirror those in plasma and are primarily mediated by IgG antibodies. J Virol. 2011;85:9555–67.PubMedCrossRefPubMedCentralGoogle Scholar
  8. Fouda GG, Mahlokozera T, Salazar-Gonzalez JF, Salazar MG, Learn G, Kumar SB, Dennison SM, Russell E, Rizzolo K, Jaeger F, Cai F, Vandergrift NA, Gao F, Hahn B, Shaw GM, Ochsenbauer C, Swanstrom R, Meshnick S, Mwapasa V, Kalilani L, Fiscus S, Montefiori D, Haynes B, Kwiek J, Alam SM, Permar SR. Postnatally-transmitted HIV-1 envelope variants have similar neutralization-sensitivity and function to that of nontransmitted breast milk variants. Retrovirology. 2013;10:3.PubMedCrossRefPubMedCentralGoogle Scholar
  9. Geijtenbeek TB, Kwon DS, Torensma R, van Vliet SJ, van Duijnhoven GC, Middel J, Cornelissen IL, Nottet HS, KewalRamani VN, Littman DR, Figdor CG, van Kooyk Y. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell. 2000;100:587–97.PubMedCrossRefGoogle Scholar
  10. Goodenow MM, Collman RG. HIV-1 coreceptor preference is distinct from target cell tropism: a dual-parameter nomenclature to define viral phenotypes. J Leuk Biol. 2006;80:965–72.CrossRefGoogle Scholar
  11. Haase AT. Targeting early infection to prevent HIV-1 mucosal transmission. Nature. 2010;464:217–23.PubMedCrossRefGoogle Scholar
  12. Hladik F, McElrath MJ. Setting the stage: host invasion by HIV. Nat Rev Immunol. 2008;8:447–57.PubMedCrossRefPubMedCentralGoogle Scholar
  13. Keele BF, Giorgi EE, Salazar-Gonzalez JF, Decker JM, Pham KT, Salazar MG, Sun C, Grayson T, Wang S, Li H, Wei X, Jiang C, Kirchherr JL, Gao F, Anderson JA, Ping LH, Swanstrom R, Tomaras GD, Blattner WA, Goepfert PA, Kilby JM, Saag MS, Delwart EL, Busch MP, Cohen MS, Montefiori DC, Haynes BF, Gaschen B, Athreya GS, Lee HY, Wood N, Seoighe C, Perelson AS, Bhattacharya T, Korber BT, Hahn BH, Shaw GM. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci U S A. 2008;105:7552–7.PubMedCrossRefPubMedCentralGoogle Scholar
  14. Kishko M, Somasundaran M, Brewster F, Sullivan JL, Clapham PR, Luzuriaga K. Genotypic and functional properties of early infant HIV-1 envelopes. Retrovirology. 2011;8:67.PubMedCrossRefPubMedCentralGoogle Scholar
  15. Kwong PD, Wyatt R, Robinson J, Sweet RW, Sodroski J, Hendrickson WA. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature. 1998;393:648–59.PubMedCrossRefGoogle Scholar
  16. Le Tortorec A, Dejucq-Rainsford N. HIV infection of the male genital tract–consequences for sexual transmission and reproduction. Int J Androl. 2010;33:e98–108.PubMedCrossRefPubMedCentralGoogle Scholar
  17. Munch J, Rucker E, Standker L, Adermann K, Goffinet C, Schindler M, Wildum S, Chinnadurai R, Rajan D, Specht A, Gimenez-Gallego G, Sanchez PC, Fowler DM, Koulov A, Kelly JW, Mothes W, Grivel JC, Margolis L, Keppler OT, Forssmann WG, Kirchhoff F. Semen-derived amyloid fibrils drastically enhance HIV infection. Cell. 2007;131:1059–71.PubMedCrossRefGoogle Scholar
  18. Powers KA, Poole C, Pettifor AE, Cohen MS. Rethinking the heterosexual infectivity of HIV-1: a systematic review and meta-analysis. Lancet Inf Dis. 2008;8:553–63.CrossRefGoogle Scholar
  19. Powers KA, Ghani AC, Miller WC, Hoffman IF, Pettifor AE, Kamanga G, Martinson FE, Cohen MS. The role of acute and early HIV infection in the spread of HIV and implications for transmission prevention strategies in Lilongwe, Malawi: a modelling study. Lancet. 2011;378:256–68.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Paul Clapham
    • 1
    • 2
  • Mohan Somasundaran
    • 3
  • Katherine Luzuriaga
    • 1
    • 3
  1. 1.Program in Molecular MedicineUniversity of Massachusetts Medical SchoolWorcesterUSA
  2. 2.Department of Microbiology and Physiological SystemsUniversity of Massachusetts Medical SchoolWorcesterUSA
  3. 3.Department of PediatricsUniversity of Massachusetts Medical SchoolWorcesterUSA