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

SG Turville, JJ Santos, I Frank, PU Cameron… - Blood, 2004 - ashpublications.org
SG Turville, JJ Santos, I Frank, PU Cameron, J Wilkinson, M Miranda-Saksena, J Dable…
Blood, 2004ashpublications.org
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 …
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.
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