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J Biol Chem. 2015 Nov 6;290(45):27345-59. doi: 10.1074/jbc.M115.681338. Epub 2015 Sep 14.

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

Author information

1
From the Institute of Medical Virology, National Reference Center for Retroviruses, University of Frankfurt, 60596 Frankfurt am Main, Germany, the Department of Infectious Diseases, Virology, University of Heidelberg, 69120 Heidelberg, Germany.
2
the Institut für Laboratoriumsmedizin, Klinische Chemie und Pathobiochemie, Charité Universitätsmedizin Berlin, 12200 Berlin, Germany.
3
Biognos AB, 402 74 Göteborg, Sweden.
4
From the Institute of Medical Virology, National Reference Center for Retroviruses, University of Frankfurt, 60596 Frankfurt am Main, Germany.
5
Organic Chemistry, Department of Chemistry, Faculty of Sciences, University of Hamburg, 20146 Hamburg, Germany.
6
the AIDS Research Institute IrsiCaixa, Institut d'Investigatio en Ciencies de la Salut Germans Trias I Pujol, Universitat Autonoma de Barcelona, 08916 Barcelona, Spain.
7
the Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602.
8
the AIDS Research Institute IrsiCaixa, Institut d'Investigatio en Ciencies de la Salut Germans Trias I Pujol, Universitat Autonoma de Barcelona, 08916 Barcelona, Spain, the Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain.
9
the Departments of Pharmacology and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21218, and.
10
the College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom.
11
From the Institute of Medical Virology, National Reference Center for Retroviruses, University of Frankfurt, 60596 Frankfurt am Main, Germany, the Department of Infectious Diseases, Virology, University of Heidelberg, 69120 Heidelberg, Germany, oliver.keppler@kgu.de.

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.

KEYWORDS:

glycobiology; glycoconjugate; infectious disease; molecular modeling; retrovirus; sialic acid

PMID:
26370074
PMCID:
PMC4646371
DOI:
10.1074/jbc.M115.681338
[Indexed for MEDLINE]
Free PMC Article

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