ABSTRACT

Turville, Stuart G., John J. Santos, Ines Frank, Paul U. Cameron, John Wilkinson, Monica Miranda-Saksena, Joanne Dable, Hella Stössel, Nikolaus Romani, Michael Piatak, Jr., Jeffrey D. Lifson, Melissa J. Pope, and Anthony L. Cunningham. 2004. “Immunodeficiency virus uptake, turnover, and 2-phase transfer in human dendritic cells,” Blood 103(6): 2170–2179. (offsite link)

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.

Return to Transmission of Immunodeficiency Viruses project page

---