Figure 1.
HIV-1 binding to DC receptors.
A. HIV-1 can bind to DC-SIGN via recognition of the viral envelope glycoprotein. B. Several gangliosides in the HIV-1 lipid membrane expose a sialyllactose moiety, while GM4 only carries sialic acid on galactose. C. Siglec-1 can capture HIV-1 through recognition of sialyllactose moieties of viral membrane gangliosides. Abbreviations: Cer (ceramide), Gal (galactose), GalNAc (N-acetylgalactosamine), Glu (glucose), SiA (sialic acid).
Figure 2.
Trans and cis recognition of Siglec-1 ligands.
A. Siglec-1 has 16 C2-type domains that extend the V-set domain from the glycocalix of the cell, allowing for recognition of sialylated molecules on different ligands and pathogens such as HIV-1. B. Other members of the Siglec family display a lower number of C2-type domains and interact only in cis, with sialylated molecules exposed on the membrane of the same cell.
Figure 3.
HIV-1 and exosome targeting to Siglec-1.
A. HIV-1 binds to Siglec-1 through viral membrane gangliosides. Viral capture is followed by accumulation in a storage compartment until virus is released to infect a contacting CD4+ T cell via viral envelope glycoprotein and CD4/coreceptor interactions. B. Exosomes bearing processed antigens on MHC II molecules bind to Siglec-1 through recognition of their membrane gangliosides. They accumulate in the same storage compartment as HIV-1 until they are released and recognized by a CD4+ T cell via the interaction of the antigen-loaded MHC II on the exosome with an antigen-specific T-cell receptor on the target cell.
Figure 4.
Immune activating signals can induce Siglec-1 expression and contribute to HIV-1 trans-infection.
A. Human genital mucosal epithelial cells produce TSL in response to HIV-1. This cytokine could induce maturation of Langerhans cells or dermal DCs in the mucosa. B. Increased translocation of bacteria from the intestinal lumen after HIV-1 infection augments LPS levels that can stimulate DCs systemically. C. HIV-1-infected plasmacytoid DCs produce interferon α in lymphoid tissues, which triggers maturation of bystander DCs and induces Siglec-1 expression. Abbreviations: LC (Langerhans cells), pDC (plasmacytoid DC) TLR (toll-like receptor), TSL (thymic stromal lymphopoietin).