(6) HIV-1 ja mannoosia sitova lektiini, komplementtil

Proc Natl Acad Sci U S A. 2011 Aug 23;108(34):14079-84. Epub 2011 Jul 28. Designed oligomers of cyanovirin-N show enhanced HIV neutralization.

Keeffe JR, Gnanapragasam PN, Gillespie SK, Yong J, Bjorkman PJ, Mayo SL.

Source

Division of Biology, Howard Hughes Medical Institute, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.

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.

PMID:

21799112

[PubMed - indexed for MEDLINE]

PMCID: PMC3161612

[Available on 2012/2/23]