Designed oligomers of cyanovirin-N show enhanced HIV neutralization
2011
Keeffe, Jennifer R. | Gnanapragasam, Priyanthi N. P. | Gillespie, Sarah K. | Yong, John | Bjorkman, Pamela J. | Mayo, Stephen L.
Cyanovirin-N (CV-N) is a small, cyanobacterial lectin that neutralizes many enveloped viruses, including human immunodeficiency virus type I (HIV-1). This antiviral activity is attributed to two homologous carbohydrate binding sites that specifically bind high mannose glycosylation present on envelope glycoproteins such as HIV-1 gp120. We created obligate CV-N oligomers to determine whether increasing the number of binding sites has an effect on viral neutralization. A tandem repeat of two CV-N molecules (CVN2) increased HIV-1 neutralization activity by up to 18-fold compared to wild-type CV-N. In addition, the CVN2 variants showed extensive cross-clade reactivity and were often more potent than broadly neutralizing anti-HIV antibodies. The improvement in activity and broad cross-strain HIV neutralization exhibited by these molecules holds promise for the future therapeutic utility of these and other engineered CV-N variants.
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