Blood Journal
Leading the way in experimental and clinical research in hematology

Immunodeficiency virus uptake, turnover, and 2-phase transfer in human dendritic cells

  1. Stuart G. Turville,
  2. John J. Santos,
  3. Ines Frank,
  4. Paul U. Cameron,
  5. John Wilkinson,
  6. Monica Miranda-Saksena,
  7. Joanne Dable,
  8. Hella Stössel,
  9. Nikolaus Romani,
  10. Michael Piatak Jr,
  11. Jeffrey D. Lifson,
  12. Melissa Pope, and
  13. Anthony L. Cunningham
  1. From the Centre For Virus Research, Westmead Millennium Institute, Sydney, Australia; Center for Biomedical Research, Population Council, New York, NY; Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia; the Department of Dermatology and Venereology, University of Innsbruck, Austria; and the AIDS Vaccine Program, Science Applications International Corporation (SAIC)–Frederick, National Cancer Institute at Frederick, Frederick, MD.

Abstract

HIV-1 subverts antigen processing in dendritic cells (DCs) resulting in viral uptake, infection, and transfer to T cells. Although DCs bound monomeric gp120 and HIV-1 similarly, virus rarely colocalized with endolysosomal markers, unlike gp120, suggesting HIV-1 alters endolysosomal trafficking. Virus within DC intracellular compartments rapidly moved to DC-CD4+ lymphocyte synapses when introduced to CD4+ lymphocyte cultures. Although viral harboring and transfer from nonlysosomal compartments was transient, given DC-associated virus protein, nucleic acids, and infectious HIV-1 transfer to CD4+, lymphocytes decayed within 24 hours. However a second long-term transfer phase was apparent in immature DCs after 48 hours as a zidovudine-sensitive rise in proviral DNA. Therefore, DCs transfer HIV-1 to CD4+ lymphocytes in 2 distinct phases. Immature and mature DCs first divert virus from the endolysosomal pathway to the DC–T-cell synapse. Secondly, the later transfer phase from immature DCs is through de novo HIV-1 production. Thus, the controversy of DCs being infected or not infected for the mechanics of viral transfer to CD4+ lymphocytes can be addressed as a function of time.

  • Submitted September 15, 2003.
  • Accepted October 17, 2003.
View Full Text