Clustered high-mannose-type N-glycans (HM-glycans)

Clustered high-mannose-type N-glycans are dense arrays of oligomannose structures found on the surface of specific viral glycoproteins, most prominently the HIV-1 envelope protein gp120 (Crispin et al., 2018, Immunity). While high-mannose glycans are typically transient intermediates in human protein glycosylation, the high density of glycans on certain viruses prevents processing enzymes from converting them into complex sugars, resulting in a persistent mannose patch (Doores, 2015, FEBS Letters). This cluster functions as a glycan shield that hides underlying protein epitopes from the host immune system, facilitating viral persistence. However, this unique density allows for the specific binding of broadly neutralizing antibodies (bnAbs) and certain lectins, which do not typically bind to the more sparse high-mannose glycans found on host cells (Scanlan et al., 2002, J. Virol.). Consequently, these clusters are a primary focus for the development of HIV vaccines and entry-inhibitor therapies designed to neutralize the virus and prevent infection (Watanabe et al., 2019, Nature Communications).

Other names

Mannose patchOligomannose-type N-glycansHigh-mannose glycan shieldMan9GlcNAc2 clustersViral glycan shield

Binding to the dense glycan cluster on viral envelopes to sterically block receptor binding or prevent the conformational changes necessary for viral-cell membrane fusion.