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

• Verfasst von: Erikson, Elina [VerfasserIn]
• Verfasst von: Wratil, Paul R. [VerfasserIn]
• Verfasst von: Frank, Martin [VerfasserIn]
• Verfasst von: Ambiel, Ina [VerfasserIn]
• Verfasst von: Pahnke, Katharina [VerfasserIn]
• Verfasst von: Pino, Maria [VerfasserIn]
• Verfasst von: Azadi, Parastoo [VerfasserIn]
• Verfasst von: Izquierdo-Useros, Nuria [VerfasserIn]
• Verfasst von: Martinez-Picado, Javier [VerfasserIn]
• Verfasst von: Meier, Chris [VerfasserIn]
• Verfasst von: Schnaar, Ronald L. [VerfasserIn]
• Verfasst von: Crocker, Paul R. [VerfasserIn]
• Verfasst von: Reutter, Werner [VerfasserIn]
• Verfasst von: Keppler, Oliver Till [VerfasserIn]
• Titel: Mouse siglec-1 mediates trans-infection of surface-bound murine leukemia virus in a sialic acid N-acyl side chain-dependent manner
• Verf.angabe: 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
• E-Jahr: 2015
• Jahr: September 14, 2015
• Umfang: 15 S.
• Fussnoten: Gesehen am 16.07.2020
• Titel Quelle: Enthalten in: The journal of biological chemistry
• Ort Quelle: Bethesda, Md. : ASBMB Publications, 1905
• Jahr Quelle: 2015
• Band/Heft Quelle: 290(2015), 45, Seite 27345-27359
• ISSN Quelle: 1083-351X
• DOI: doi:10.1074/jbc.M115.681338
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: glycobiology
• Sach-SW: glycoconjugate
• Sach-SW: infectious disease
• Sach-SW: molecular modeling
• Sach-SW: retrovirus
• Sach-SW: sialic acid
• K10plus-PPN: 1725016737

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.