1. Mouse Siglec-1 Mediates trans-Infection of Surface-bound Murine Leukemia Virus in a Sialic Acid N-Acyl Side Chain-dependent Manner.
- Author
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Erikson E, Wratil PR, Frank M, Ambiel I, Pahnke K, Pino M, Azadi P, Izquierdo-Useros N, Martinez-Picado J, Meier C, Schnaar RL, Crocker PR, Reutter W, and Keppler OT
- Subjects
- Animals, Binding Sites, Cell Line, Gangliosides chemistry, Gangliosides metabolism, Host-Pathogen Interactions physiology, Humans, Interferon-alpha physiology, Leukemia, Experimental physiopathology, Leukemia, Experimental virology, Lymphocytes physiology, Lymphocytes virology, Macrophages physiology, Mice, Mice, Inbred C57BL, Mice, Knockout, Models, Molecular, Moloney murine leukemia virus genetics, Moloney murine leukemia virus physiology, N-Acetylneuraminic Acid chemistry, Receptors, Virus chemistry, Receptors, Virus physiology, Retroviridae Infections physiopathology, Retroviridae Infections virology, Sialic Acid Binding Ig-like Lectin 1 genetics, Tumor Virus Infections physiopathology, Tumor Virus Infections virology, Moloney murine leukemia virus pathogenicity, Sialic Acid Binding Ig-like Lectin 1 chemistry, Sialic Acid Binding Ig-like Lectin 1 physiology
- 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., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)
- Published
- 2015
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