Mouse Siglec-1 Mediates trans-Infection of Surface-bound Murine Leukemia Virus in a Sialic Acid N-Acyl Side Chain-dependent Manner.

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. 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.

• Authors: 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, Oliver T Keppler
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 290 Issue 45 Pg. 27345-27359 (Nov 06 2015) ISSN: 1083-351X [Electronic] United States
• PMID: 26370074 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• Gangliosides
• Interferon-alpha
• Receptors, Virus
• Sialic Acid Binding Ig-like Lectin 1
• Siglec1 protein, mouse
• N-Acetylneuraminic Acid

Topics

• Animals
• Binding Sites
• Cell Line
• Gangliosides (chemistry, metabolism)
• Host-Pathogen Interactions (physiology)
• Humans
• Interferon-alpha (physiology)
• Leukemia, Experimental (physiopathology, virology)
• Lymphocytes (physiology, virology)
• Macrophages (physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Models, Molecular
• Moloney murine leukemia virus (genetics, pathogenicity, physiology)
• N-Acetylneuraminic Acid (chemistry)
• Receptors, Virus (chemistry, physiology)
• Retroviridae Infections (physiopathology, virology)
• Sialic Acid Binding Ig-like Lectin 1 (chemistry, genetics, physiology)
• Tumor Virus Infections (physiopathology, virology)