Session 46Poster Presentations DC-SIGN and Related Molecules Session Day and Time: Thursday 1:30 - 3:30 pm Room: Hall D
363 Role of pH in the DC-SIGN/HIV Interaction C. Davis*, S. Pöhlmann, G. Leslie, F. Baribaud, R. Doms Univ of Pennsylvania Sch of Med, Philadelphia
Background: DC-SIGN, a type II membrane protein with a C-type (calcium dependent) lectin domain that is highly expressed on mucosal dendritic cells (DCs) and certain macrophages in vivo, binds to the glycoproteins of human and simian immunodeficiency viruses (HIV and SIV), Ebola virus, and Hepatitis C virus. HIV captured by DC-SIGN can be presented to T-cells, resulting in efficient virus infection in trans, perhaps representing a mechanism by which virus can be ferried via normal DC trafficking from mucosal tissues to lymphoid organs in vivo. Recently, it has been shown that DC-SIGN-mediated HIV internalization and transport into low pH compartments may be important for efficient transmission. To further address the mechanism by which internalization contributes to HIV transmission we have analyzed the pH dependence of the DC-SIGN/HIV interaction.
Methods: Binding of purified, monomeric HIV gp120 to DC-SIGN expressing cells was analyzed at different pH values in a FACS based assay as well as by western blot. In parallel we investigated the pH dependence of HIV binding and transmission by DC-SIGN positive cells.
Results: We found that the binding of monomeric gp120 to DC-SIGN was greatly reduced after incubation at mild acidic pH. In agreement with these data, exposure to low pH reduced both the binding and the transmission of HIV particles by various DC-SIGN expressing cell lines by about 75%.
Conclusions: Our data suggest that upon internalization and transport into low pH compartments HIV is released from DC-SIGN. Release of HIV from DC-SIGN might allow HIV to avoid degradation and be recycled back to the surface where it can be transmitted to receptor positive cells.
