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Designed oligomers of cyanovirin-N show enhanced HIV neutralization.


ABSTRACT: 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 (CVN(2)) increased HIV-1 neutralization activity by up to 18-fold compared to wild-type CV-N. In addition, the CVN(2) 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.

SUBMITTER: Keeffe JR 

PROVIDER: S-EPMC3161612 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Designed oligomers of cyanovirin-N show enhanced HIV neutralization.

Keeffe Jennifer R JR   Gnanapragasam Priyanthi N P PN   Gillespie Sarah K SK   Yong John J   Bjorkman Pamela J PJ   Mayo Stephen L SL  

Proceedings of the National Academy of Sciences of the United States of America 20110728 34


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  ...[more]

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