Mouse Siglec-1 mediates trans-infection of surface-bound murine leukemia virus in a sialic acid N-acyl side chain-dependent manner

Mouse Siglec-1 mediates trans-infection of surface-bound murine leukemia virus in a sialic acid N-acyl side chain-dependent manner

Data de publicació online: 14/09/2015 Data de publicació en paper: 6 Novembre 2015 Revista: Journal of Biological Chemistry

Abstract:

Siglec-1 (sialoadhesin, CD169) is a surface receptor on human cells that mediates trans-enhancement of HIV-1 infection through recognition of sialic acid moieties in virus membrane gangliosides. Here we demonstrate that mouse Siglec-1, expressed on the surface of primary macrophages in an interferon-α-responsive manner, captures murine leukemia virus (MLV) particles and mediates their transfer to proliferating lymphocytes. The MLV infection of primary B-cells was markedly more efficient than that of primary T-cells. Early after virus exposure of macrophages, MLV Gag frequently co-localized with Siglec-1 and trans-infection, primarily of surface-bound MLV particles, efficiently occurred. To explore the role of sialic acid for MLV trans-infection at a submolecular level, we analyzed the potential of six sialic acid precursor analogs to modulate the sialylated ganglioside-dependent interaction of MLV particles with Siglec-1. Biosynthetically engineered sialic acids were detected in both the glycolipid and glycoprotein fractions of MLV producer cells. MLV released from cells carrying N-acyl-modified sialic acids displayed strikingly different capacities for Siglec-1-mediated capture and trans-infection: N-butanoyl, N-isobutanoyl, N-glycolyl, or N-pentanoyl side chain modifications resulted in up to 92% and 80% reduction of virus particle capture and trans-infection, respectively, while N-propanoyl or N-cyclopropylcarbamyl side chains had no effect. In agreement with these functional analyses, molecular modeling indicated reduced binding affinities for non-functional N-acyl modifications. Thus, Siglec-1 is a key receptor for macrophage/lymphocyte trans-infection of surface-bound virions and the N-acyl side chain of sialic acid is a critical functional determinant for the Siglec-1-MLV interaction.Read article online.

Autors: Elina Erikson, Paul R. Wratil, Martin Frank, Ina Ambiel, Katharina Pahnke, Maria Pino Claveria, Parastoo Azadi, Nuria Izquierdo-Useros, Javier Martinez-Picado, Chris Meier, Ronald L. Schnaar, Paul R. Crocker, Werner Reutter and Oliver T. Keppler.

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