Summary auto-generated
This study investigates how human cytomegalovirus (HCMV) binds to carbohydrate structures on host cell surfaces. Using thin-layer chromatography and solid-phase binding assays, researchers found that HCMV strongly binds to sulfated glucuronyl glycosphingolipids (SGGLs), particularly sulfated glucuronyl lactosaminylparagloboside (SGLPG). The virus showed weaker binding to other sulfated glycolipids and to glycolipids containing repeating lactosamine units without sulfation. When virus particles were pre-incubated with these glycolipids, both immediate-early gene expression and plaque formation were inhibited, with effects correlating to binding strength. Treatment of host cells with HNK-1 monoclonal antibody, which recognizes the specific sulfated carbohydrate epitope on SGGLs, partially blocked HCMV infection. The research demonstrates that HCMV recognizes specific sulfated carbohydrate structures and suggests this binding plays an important role in viral attachment and entry during infection. The findings correlate with previous observations that HCMV-infected patients develop antibodies against SGGLs.
Key findings
- HCMV binds most strongly to sulfated glucuronyl lactosaminylparagloboside (SGLPG), which contains both 3-O-sulfated glucuronyl moieties and repeating lactosamine structures
- Binding to sulfated glycolipids specifically inhibits HCMV immediate-early gene expression and plaque formation in a dose-dependent manner
- The repeating lactosamine structure (-3Galβ1–4GlcNAc-)₂ combined with 3-O-sulfated saccharide is critical for HCMV recognition and binding
- HNK-1 monoclonal antibody targeting the sulfated carbohydrate epitope partially blocks HCMV infection of host cells
- Inhibitory effects of glycolipids on HCMV infection correlate strongly with their binding abilities to the virus
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Abstract
Interactions between human cytomegalovirus (HCMV) and various carbohydrate structures were analysed using sulfated glucuronyl glycosphingolipids (SGGLs) and the structurally related glycosphingolipids (GLs). A thin-layer chromatography-overlay assay and a solid-phase binding assay revealed that HCMV strongly bound to sulfated glucuronyl lactosaminylparagloboside, one of the SGGLs having the repeating lactosamine structure (3Gal beta1-4GlcNAc1-)2 in addition to the 3-O-sulfated glucuronyl moiety. The virus bound less strongly to other 3-O-sulfated GLs, which included sulfated glucuronyl paragloboside and cerebroside sulfate ester, and also to (3Gal beta1- 4GlcNAc1-)2-containing GLs that included nLc6Cer. Thus, a (3Gal beta1- 4GlcNAc1-)2 and a 3-O-sulfated saccharide seem to be important structures for the binding by HCMV. When virus particles were preincubated with these GLs, inhibitory effects were observed both on expression of the viral immediate-early gene and on plaque formation by HCMV. These effects were very well correlated with the abilities of the GLs to bind to the virus. Pretreatment of host cells with HNK-1 monoclonal antibody, which specifically recognizes SGGLs, resulted in partial inhibition of plaque formation by HCMV. These results clearly show that HCMV recognizes and binds to the sulfated carbohydrate structure in SGGL and also suggest that binding of HCMV to the specific sugar structure may play an important role in HCMV infection.