Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letters to the Editor
  • Published:

AIDS models: Microbicides could learn from vaccines

Nature Medicine volume 8, page 425 (2002)Cite this article

To the editor

The importance of using biologically relevant challenge virus in non-human primate vaccine studies was recently highlighted in the commentary by Feinberg and Moore1, published in the March issue of Nature Medicine. These issues are equally important in the development of effective anti-HIV-1 microbicides, in particular those based on negatively charged, sulphated polyanions. A number of these, including Carraguard, PRO2000 and dextrin-2-sulphate (D2S) are poised to enter phase 2/3 trials. Two such compounds, PRO2000 and D2S, have been shown to offer protection in macaques against vaginal challenge with simian-human inmmunodeficiency virus 89.6P (SHIV-89.6P)2, which exclusively uses CXCR4 as its coreceptor. The inhibitory effect of these polyanions probably reflects their interaction with positively charged regions on the viral gp120 glycoprotein, particularly the V3-loop region3. This interaction may be sufficiently strong to render the virus noninfectious within the vaginal lumen before contact with susceptible target cells. This would provide protection even in the event of passive, or active (through uptake by migratory dendritic cells) transport of virus away from inhibitory concentrations of the microbicide4. However, the positive charge on the gp120 protein of CXCR4-using (X4) viruses is significantly greater than that of the R5 viruses, which use the CCR5 coreceptor for entry3. This factor may render X4 viruses relatively sensitive to sulphated polyanions, compared with their R5 counterparts. There is little or no direct binding of polyanions to gp120 of R5 viruses before CD4 engagement, although conformational changes induced by CD4 binding expose regions in gp120 that are more basic in charge; the exposure of these sites may now render the virus susceptible to the action of polyanions5.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

References

  1. Feinberg, M.B. & Moore, J.P. AIDS vaccine models: Challenging challenge viruses. Nature Med. 8 207–210 (2002).

    Article  CAS  Google Scholar 

  2. Weber, J. et al. 'Chemical condoms' for the prevention of HIV infection: evaluation of novel agents against SHIV(89.6PD) in vitro and in vivo. AIDS. 15, 1563–1568 (2001).

  3. Moulard, M. et al. Selective interactions of polyanions with basic surfaces on human immunodeficiency virus type 1 gp120. J. Virol. 74, 1948–1960 (2000).

    Article  CAS  Google Scholar 

  4. Baribaud, F., Pohlmann, S. & Doms, R.W. The role of DC-SIGN and DC-SIGNR in HIV and SIV attachment, infection, and transmission. Virology 286, 1–6 (2001).

    Article  CAS  Google Scholar 

  5. Doms, R.W. & Trono, D. The plasma membrane as a combat zone in the HIV battlefield. Genes Dev. 14, 2677–2688 (2000).

    Article  CAS  Google Scholar 

  6. Greenhead, P. et al. Parameters of human immunodeficiency virus infection of human cervical tissue and inhibition by vaginal virucides. J. Virol. 74, 5577–5586 (2000).

    Article  CAS  Google Scholar 

  7. Harouse, J.M., Gettie, A., Tan, R.C., Blanchard, J. & Cheng-Mayer, C. Distinct pathogenic sequela in rhesus macaques infected with CCR5 or CXCR4 utilizing SHIVs. Science 284, 816–819 (1999).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Infectious Diseases St George's Hospital Medical School, London, UK

    Robin J. Shattock

  2. Department of Microbiology, University of Pennsylvania, Philadelphia, USA

    Robert W. Doms

Authors
  1. Robin J. Shattock
    View author publications

    Search author on:PubMed Google Scholar

  2. Robert W. Doms
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shattock, R., Doms, R. AIDS models: Microbicides could learn from vaccines. Nat Med 8, 425 (2002). https://doi.org/10.1038/nm0502-425

Download citation

  • Issue date:

  • DOI: https://doi.org/10.1038/nm0502-425

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing