title: 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.
authors.affiliation: Division of Biology, Howard Hughes Medical Institute, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Keeffe
authors.forename: Priyanthi N P
authors.initials: PN
authors.lastname: Gnanapragasam
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Gillespie
authors.forename: John
authors.initials: J
authors.lastname: Yong
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Bjorkman
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Mayo
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry* / Q000276:immunology* / Q000494:pharmacology; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000276:immunology* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D015483:HIV Antibodies / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D009500:Neutralization Tests; D055503:Protein Multimerization / Q000187:drug effects; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012996:Solutions
chemical_list: D019380:Anti-HIV Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D015483:HIV Antibodies; D050505:Mutant Proteins; D012996:Solutions; C107733:cyanovirin N