ZBiotech’s glycosaminoglycan microarray helps researchers specify host sugar substrates for cytomegalovirus entry.

Glycosaminoglycan is a linear sugar molecule found on most animal cells and serves as binding substrates for many protein ligands, such as growth factors, morphogens, and chemokines. Consequently, these sugars regulate various biological processes, such as angiogenesis, blood coagulation, and tumor metastasis. However, these sugars also serve as entry receptors for pathogens. For example, glycosaminoglycans are substrates for human papillomavirus, SARS-CoV-2, hepatitis-C virus, and human cytomegalovirus (HCMV). Viral particles attach to the glycosaminoglycans, leading to several reactions that result in the fusion of the viral envelope with the host cell membrane, after which the viral genomic material enters the cell. Mitra and colleagues found that HCMV virions preferentially bind to sulfated long-chain heparan sulfate (HS). Especially, HSs with higher sulfate saturation tend to be better binders. Moreover, HCMV entry was compromised in cells that lacked the enzyme glucosaminyl sulfotransferase that catalyzes HS synthesis.

Mitra and colleagues evaluated which type of glycosaminoglycans preferentially binds to the HCMV virions by using our Glycosaminoglycan Microarray. In this study, diluted HCMV virions were applied to the arrays in a series of concentrations. After staining with primary and secondary antibodies, bindings between glycosaminoglycans and HCMV virions were detected.

Using our microarray, the researchers have found that HCMV virions significantly bind to all tested HS sugars, and the binding was stronger as their degree of polymerization increased. HCMVs also interacted with large-sized chondroitin sulfate D and dermatan sulfate oligosaccharides. However, no binding was observed between HCMV virions and non-sulfated hyaluronic acid or chondroitin sulfate AC. The overall best binder of HCMVS was heparin. Therefore, the researchers used our Heparan Sulfate Glycan Array to further test the binding of HCMV virions to different forms of heparan sulfates. The experiment revealed that HCMVs bind the strongest to heparan sulfates with longer monosaccharide chains with moderate sulfation. The binding was minimal to unsulfated glycans, indicating that sulfation and a higher degree of polymerization are critical determinants of heparan sulfates for HCMV binding.

The Glycosaminoglycan Microarray is a valuable tool for evaluating interactions between glycosaminoglycans and viral particles. Our Glycosaminoglycan Microarray features several glycosaminoglycans varying in length, degrees of sulfation, and disaccharide sequences. With the aid of our Heparan Sulfate Glycan Array, our glycosaminoglycan–based microarray products can assist researchers in comprehensively evaluating such interactions.