Glycosylation, Hypogammaglobulinemia, and Resistance to Viral Infections

In two siblings, a congenital disorder of glycosylation (CDG-IIb) was shown to lead to severe hypogammaglobulinemia but paradoxically impaired viral replication. Most proteins, including immunoglobulins, human virus receptors, and viral-coded proteins, are post-translationally modified with sugars or sugar chains that are generically referred to as glycans. Glycans are primarily classified as N-linked or O-linked oligosaccharides, depending on whether they are bound to the amide group of asparagine (N-linked) or the hydroxyl group of serine or threonine (O-linked). Glycans are associated with protein conformation, folding, solubility, stability, half-life, and antigenicity and are the moieties recognized by glycan-binding proteins. The congenital disorders of glycosylation (CDGs) are genetic disorders affecting the N-glycosylation process. CDGs are divided into defects in the synthesis of N-glycans (CDG-I) . . .