The anti-HIV cyanovirin-N domain is evolutionarily conserved and occurs as a protein module in eukaryotes.

A novel protein family homologous to the sugar-binding antiviral protein cyanovirin-N (CVN) is described. CVN, an 11-kDa protein that, by binding to the high-mannose moiety of certain viral surface glycoproteins, blocks virus entry into target cells, has thus far been identified only in the cyanobacterium Nostoc ellipsosporum. Here we show that CVN belongs to a protein family identified by analysis of transcript sequences deriving from a gene expression profiling study conducted in the truffle Tuber borchii. Members of this family (named CyanoVirin-N Homology) are found in filamentous ascomycetes and in the fern Ceratopteris richardii. As revealed by 3D structure-based searches, all CVNH proteins have a predicted fold that matches the so far unique fold of the cyanobacterial polypeptide. The CVNH domain is a versatile protein module. In ferns and cyanobacteria it is found in secretory proteins. In filamentous ascomycetes it is found in nonsecretory monodomain proteins as well as part of multidomain proteins bearing functionally related modules such as the peptidoglycan and chitin-binding domain LysM. Transcript abundance data further indicate that the expression of different CVNH forms is modulated in response to nutrient availability. These findings have implications for the understanding of protein-oligosaccharide interaction in fungi and plants, and provide candidate polypeptides to be tested and exploited as antiviral agents.