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Session 11 Symposium
Virus-Host Cell Synapses
Monday, 4–6 pm
Room 2008
43
Virus Capture and Transmission by Dendritic Cells
Anthony L Cunningham*1,2 , S G Turville1,2, J Wilkinson1,2, J Santos3, I Frank3, P Cameron2, J Dable1,2, D Hart6, N Romani4, J D Lifson5 , and M Pope3
1Ctr for Virus Res, Westmead, Australia; 2Westmead Millennium Inst, Sydney, Australia; 3Ctr for Biomed Res, Population Council, New York, NY, USA; 4Univ of Innsbruck, Austria; 5NCI at Frederick, MD, USA; and 6MaterMed Res Inst, Queensland, Australia

Background: Dendritic cells play a major role in HIV pathogenesis. Epithelial dendritic cells appear to be one of the first cells infected after sexual transmission and transfer of the virus to CD4 lymphocytes, simultaneously activating these cells to produce high levels of HIV replication. Such transfer may occur locally in inflamed mucosa or after dendritic cells have matured and migrated to local lymph nodes. HIV binds to C-type lectin receptors (CLR) on epithelial and monocyte-derived (MD) dendritic cells (DC), probably Langerin or Langerhans cells and mannose receptor and DC-SIGN on dermal DC and MDDC. These CLR facilitate uptake into endosomes, where HIV undergoes rapid acid proteolytic degradation over 24 hours, or transfer to CD4/CCR5 entry pathway followed by slow low-level replication.

Results: After contact with CD4 lymphocytes, immature DC were shown to transfer HIV-1 to these cells in 2 distinct phases. In the first 24 hours, virus was diverted from the endolysosomal pathway to the DC-T-cell synapse, but later transfer was from de novo HIV-1 production by DC.

Conclusions: Both phases may have a role in vivo, especially in transfer to infiltrating CD4 lymphocytes in inflamed mucosa. However, the low-level infection of immature dendritic cells may be more important as it leads to R5 HIV strain selection and persistence of virus within dendritic cells for over 24 hours, sufficient for these infected DC to transit to lymph nodes.

Keywords: antiretroviral therapy; peripheral nervous system diseases; mitochondrial DNA