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