Designed oligomers of cyanovirin-N show enhanced HIV neutralization

作者：Keeffe Jennifer R; Gnanapragasam Priyanthi N P; Gillespie Sarah K; Yong John; Bjorkman Pamela J; Mayo Stephen L^*

来源：Proceedings of the National Academy of Sciences, 2011, 108(34): 14079-14084.

DOI：10.1073/pnas.1108777108

• crystal structure
• domain-swapped dimer
• protein engineering

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.

• 出版日期2011-8-23