TY  - JOUR
A1  - Erikson, Elina
A1  - Wratil, Paul Robin
A1  - Frank, Martin
A1  - Ambiel, Ina
A1  - Pahnke, Katharina
A1  - Pino, Maria
A1  - Azadi, Parastoo
A1  - Izquierdo-Useros, Nuria
A1  - Martinez-Picado, Javier
A1  - Meier, Chris
A1  - Schnaar, Ronald L.
A1  - Crocker, Paul R.
A1  - Reutter, Werner
A1  - Keppler, Oliver Till
T1  - Mouse siglec-1 mediates trans-infection of surface-bound murine leukemia virus in a sialic acid N-acyl side chain-dependent manner
T2  - Journal of biological chemistry
N2  - 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.
KW  - glycobiology
KW  - glycoconjugate
KW  - infectious disease
KW  - molecular modeling
KW  - retrovirus
KW  - sialic acid
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/77195
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-771957
SN  - 0021-9258
VL  - 290.2015
IS  - 45
SP  - 27345
EP  - 27359
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -