Elina Erikson, Paul Robin 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 Till Keppler
- 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.
MetadatenVerfasserangaben: | Elina EriksonGND, Paul Robin WratilGND, Martin FrankORCiD, Ina Ambiel, Katharina PahnkeORCiDGND, Maria PinoORCiDGND, Parastoo AzadiORCiD, Nuria Izquierdo-UserosORCiDGND, Javier Martinez-PicadoORCiD, Chris MeierGND, Ronald L. SchnaarORCiDGND, Paul R. CrockerGND, Werner ReutterGND, Oliver Till KepplerORCiDGND |
---|
URN: | urn:nbn:de:hebis:30:3-771957 |
---|
DOI: | https://doi.org/10.1074/jbc.M115.681338 |
---|
ISSN: | 0021-9258 |
---|
Pubmed-Id: | https://pubmed.ncbi.nlm.nih.gov/26370074 |
---|
Titel des übergeordneten Werkes (Englisch): | Journal of biological chemistry |
---|
Verlag: | American Society for Biochemistry and Molecular Biology Publications |
---|
Verlagsort: | Bethesda, Md |
---|
Dokumentart: | Wissenschaftlicher Artikel |
---|
Sprache: | Englisch |
---|
Datum der Veröffentlichung (online): | 04.01.2021 |
---|
Jahr der Erstveröffentlichung: | 2015 |
---|
Veröffentlichende Institution: | Universitätsbibliothek Johann Christian Senckenberg |
---|
Datum der Freischaltung: | 22.04.2024 |
---|
Freies Schlagwort / Tag: | glycobiology; glycoconjugate; infectious disease; molecular modeling; retrovirus; sialic acid |
---|
Jahrgang: | 290.2015 |
---|
Ausgabe / Heft: | 45 |
---|
Seitenzahl: | 15 |
---|
Erste Seite: | 27345 |
---|
Letzte Seite: | 27359 |
---|
Institute: | Medizin |
---|
DDC-Klassifikation: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
---|
| 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
---|
Sammlungen: | Universitätspublikationen |
---|
Lizenz (Deutsch): | Creative Commons - CC BY - Namensnennung 4.0 International |
---|