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.

  • Letter to the Editor
  • Published:

Adopting autologous hematopoietic stem cells with non-functional CCR5 and CXCR4 against HIV

Bone Marrow Transplantation volume 45, pages 770–771 (2010)Cite this article

As the causative agent of acquired immune deficiency syndrome (AIDS), human immunodeficiency virus type 1 (HIV-1) has exerted a formidable challenge to the biomedical research and has become one of the leading causes of death worldwide. Since its discovery at the Institut Pasteur in 1983, a quarter century of scientific efforts has been applied to designing a valid HIV vaccine, yet this object remains unattainable, mainly because of the conspicuous barrier derived from the virus. Since the introduction of combination antiretroviral therapy in 1996, treatment for HIV-1 has improved, which noticeably elevated the therapeutic effect for masses of patients who receive antiretroviral drugs. However, the optimism of antiretroviral treatment is restricted by the current impossibility of viral eradication, the sustained medication with complex regimens, the potential toxic effects, and the prevalence of drug-resistant isolates.

The co-receptor discoveries revealed that HIV-1 enters host cells by binding to a cell-surface molecule, CD4, which serves as the primary receptor and then interacting with co-receptor, either CCR5 or the CXCR4.1 According to a new classification system based on co-receptor use, HIV-1 isolates are now classified into three major groups: R5 (CCR5-tropic), X4 (CXCR4-tropic), and R5X4 (dual-tropic strains, which use both co-receptors with comparable efficiency).1 One avenue to development of effective HIV therapies is focusing on a distinct population who seem to be naturally resistant to HIV-1 infection. With the property of a stable CD4+ T-cell count and no signs of AIDS, a small percentage of HIV-seropositive individuals, termed as long-term non-progressors, were observed. This population generally remains healthy during the infected state for more than 10 years.2 Meanwhile, there is another group of people, high-risk HIV-exposed seronegative individuals who have been exposed to HIV and remain uninfected. These exposures include unprotected sexual behavior with an HIV-infected person, intravenous drug usage with a definite history of needle sharing, vertical transmission from HIV positive mothers to newborn infants, transfusions of blood or blood products contaminated with HIV, as well as persistent parenteral exposure to HIV-infected blood or body fluids.2

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

References

  1. Berger EA, Doms RW, Fenyo EM, Korber BT, Littman DR, Moore JP et al. A new classification for HIV-1. Nature 1998; 391: 240.

    Article  CAS  PubMed  Google Scholar 

  2. Shearer GM, Clerici M . Protective immunity against HIV infection: has nature done the experiment for us? Immunol Today 1996; 17: 21–24.

    Article  CAS  PubMed  Google Scholar 

  3. Smith MW, Dean M, Carrington M, Winkler C, Huttley GA, Lomb DA et al. Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Science 1997; 277: 959–965.

    Article  CAS  PubMed  Google Scholar 

  4. Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM et al. Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 1996; 382: 722–725.

    Article  CAS  PubMed  Google Scholar 

  5. Sullivan AD, Wigginton J, Kirschner D . The coreceptor mutation CCR5Δ32 influences the dynamics of HIV epidemics and is selected for by HIV. PNAS 2001; 98: 10214–10219.

    Article  CAS  PubMed  Google Scholar 

  6. Trial watch: novel HIV gene therapy enters Phase I trial. Nat Rev Drug Discov 2009; 8: 267.

  7. An DS, Donahue RE, Kamata M, Poon B, Metzger M, Mao SH et al. Stable reduction of CCR5 by RNAi through hematopoietic stem cell transplant in non-human primates. PNAS 2007; 104: 13110–13115.

    Article  CAS  PubMed  Google Scholar 

  8. Hütter G, Nowak D, Mossner M, Ganepola S, Müßig A, Allers K et al. Long-Term control of HIV by CCR5 delta32/delta32 stem-cell transplantation. N Engl J Med 2009; 360: 692–698.

    Article  PubMed  Google Scholar 

  9. Michael NL, Nelson JAE, KewalRamani VN, Chang G, O'Brien SJ, Mascola JR et al. Exclusive and persistent use of the entry coreceptor CXCR4 by human immunodeficiency virus type 1 from a subject homozygous for CCR5 Δ32. J Virol 1998; 72: 6040–6047.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Zou YR, Kottmann AH, Kuroda M, Taniuchi I, Littman DR . Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature 1998; 393: 595–599.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Microbiology and Immunology, Chengdu University of Traditional Chinese Medicine, Chengdu, China

    Y Lai

Authors
  1. Y Lai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Y Lai.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lai, Y. Adopting autologous hematopoietic stem cells with non-functional CCR5 and CXCR4 against HIV. Bone Marrow Transplant 45, 770–771 (2010). https://doi.org/10.1038/bmt.2009.201

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2009.201

Search

Advanced search

Quick links