Cover Image

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

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 interfero...

Full description

Saved in:
Bibliographic Details
Main Authors: Erikson, Elina (Author) , Wratil, Paul R. (Author) , Frank, Martin (Author) , Ambiel, Ina (Author) , Pahnke, Katharina (Author) , Pino, Maria (Author) , Azadi, Parastoo (Author) , Izquierdo-Useros, Nuria (Author) , Martinez-Picado, Javier (Author) , Meier, Chris (Author) , Schnaar, Ronald L. (Author) , Crocker, Paul R. (Author) , Reutter, Werner (Author) , Keppler, Oliver Till (Author)
Format: Article (Journal)
Language:English
Published: September 14, 2015
In: The journal of biological chemistry
Year: 2015, Volume: 290, Issue: 45, Pages: 27345-27359
ISSN:1083-351X
DOI:10.1074/jbc.M115.681338
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1074/jbc.M115.681338
Verlag, lizenzpflichtig, Volltext: http://www.jbc.org/content/290/45/27345
Get full text
Author Notes:Elina Erikson, Paul R. Wratil, Martin Frank, Ina Ambiel, Katharina Pahnke, Maria Pino, Parastoo Azadi, Nuria Izquierdo-Useros, Javier Martinez-Picado, Chris Meier, Ronald L. Schnaar, Paul R. Crocker, Werner Reutter, and Oliver T. Keppler
Description
Summary: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. The major structural protein of MLV particles, 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, whereas 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 determinant for the Siglec-1/MLV interaction.
Item Description:Gesehen am 16.07.2020
Physical Description:Online Resource
ISSN:1083-351X
DOI:10.1074/jbc.M115.681338

Similar Items