Structural Insight into Non-Enveloped Virus Binding to Glycosaminoglycan Receptors: A Review

Abstract

Viruses are infectious agents that hijack the host cell machinery in order to replicate and generate progeny. Viral infection is initiated by attachment to host cell receptors, and typical viral receptors are cell-surface-borne molecules such as proteins or glycan structures. Sialylated glycans (glycans bearing sialic acids) and glycosaminoglycans (GAGs) represent major classes of carbohydrate receptors and have been implicated in facilitating viral entry for many viruses. As interactions between viruses and sialic acids have been extensively reviewed in the past, this review provides an overview of the current state of structural knowledge about interactions between non-enveloped human viruses and GAGs. We focus here on adeno-associated viruses, human papilloma viruses (HPVs), and polyomaviruses, as at least some structural information about the interactions of these viruses with GAGs is available. We also discuss the multivalent potential for GAG binding, highlighting the importance of charged interactions and positively charged amino acids at the binding sites, and point out challenges that remain in the field.

A poly‐proline II helix in YadA from Yersinia enterocolitica serotype O:9 facilitates heparin binding through electrostatic interactions

“…In summary, we showed how a short, structured insertion in the YadA O:9 N‐terminal region aids in adhesion to heparin and thus completely alters adhesion properties compared to YadA from other Y. enterocolitica serotypes. We hence exemplify how one simple genetic event can alter virulence‐specific traits of a bacterial pathogen – a process that is typically more associated with viruses [48].…”

The Trimeric Autotransporter Adhesin YadA of Yersinia enterocolitica Serotype O:9 Binds Glycan Moieties

“…This is supported by the observation that YadA O:9 interacts not only with the glycan residues of the glycoprotein Vn but also with the carbohydrate polymer heparin. Interactions with glycans are employed by many pathogens for adhesion and invasion, especially in viruses (Marks et al, 2001;Guan et al, 2017;Sorin et al, 2021). Also, bacterial virulence factors like UpaB and Pili have been shown to interact with the glycosylations of glycoproteins and GAGs (Rajas et al, 2017;Paxman et al, 2019;Sauer et al, 2019;Vizarraga et al, 2021).…”

Bioinformatics approaches for unveiling virus-host interactions

“…Thus, the compositions of the viral nucleotide and amino acid sequences are similar to those of the host, and the compositions of viruses infecting the same host are also similar. Moreover, some studies have used the physicochemical properties of viral amino acid sequences as predictive features, which have been reported to be important for binding viral surface proteins to host receptors [26] , [27] . In particular, we present two studies that used the k -mer frequency of nucleotide or amino acid sequences as features for host-range prediction.…”