Next Article in Journal
Phylogenetic and Molecular Variability Studies Reveal a New Genetic Clade of Citrus leprosis virus C
Next Article in Special Issue
Griffithsin: An Antiviral Lectin with Outstanding Therapeutic Potential
Previous Article in Journal
Antiviral Effects of Black Raspberry (Rubus coreanus) Seed and Its Gallic Acid against Influenza Virus Infection
Article Menu

Export Article

Open AccessArticle
Viruses 2016, 8(6), 158; doi:10.3390/v8060158

A Designed “Nested” Dimer of Cyanovirin-N Increases Antiviral Activity

1
School of Molecular Sciences, Arizona State University, Tempe, AZ 85287-1604, USA
2
Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA
3
Basic Science Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, MD 21702, USA
4
Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
5
Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA
6
School of Life Sciences and The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Eric O. Freed
Received: 15 January 2016 / Revised: 26 May 2016 / Accepted: 30 May 2016 / Published: 6 June 2016
(This article belongs to the Special Issue Lectins as Antiviral)
View Full-Text   |   Download PDF [2407 KB, uploaded 7 June 2016]   |  

Abstract

Cyanovirin-N (CV-N) is an antiviral lectin with potent activity against enveloped viruses, including HIV. The mechanism of action involves high affinity binding to mannose-rich glycans that decorate the surface of enveloped viruses. In the case of HIV, antiviral activity of CV-N is postulated to require multivalent interactions with envelope protein gp120, achieved through a pseudo-repeat of sequence that adopts two near-identical glycan-binding sites, and possibly involves a 3D-domain-swapped dimeric form of CV-N. Here, we present a covalent dimer of CV-N that increases the number of active glycan-binding sites, and we characterize its ability to recognize four glycans in solution. A CV-N variant was designed in which two native repeats were separated by the “nested” covalent insertion of two additional repeats of CV-N, resulting in four possible glycan-binding sites. The resulting Nested CV-N folds into a wild-type-like structure as assessed by circular dichroism and NMR spectroscopy, and displays high thermal stability with a Tm of 59 °C, identical to WT. All four glycan-binding domains encompassed by the sequence are functional as demonstrated by isothermal titration calorimetry, which revealed two sets of binding events to dimannose with dissociation constants Kd of 25 μM and 900 μM, assigned to domains B and B’ and domains A and A’ respectively. Nested CV-N displays a slight increase in activity when compared to WT CV-N in both an anti-HIV cellular assay and a fusion assay. This construct conserves the original binding specifityies of domain A and B, thus indicating correct fold of the two CV-N repeats. Thus, rational design can be used to increase multivalency in antiviral lectins in a controlled manner. View Full-Text
Keywords: Cyanovirin-N; antiviral lectins; glycan-binding proteins; oligomannose; gp120 Cyanovirin-N; antiviral lectins; glycan-binding proteins; oligomannose; gp120
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Woodrum, B.W.; Maxwell, J.; Allen, D.M.; Wilson, J.; Krumpe, L.R.; Bobkov, A.A.; Hill, R.B.; Kibler, K.V.; O’Keefe, B.R.; Ghirlanda, G. A Designed “Nested” Dimer of Cyanovirin-N Increases Antiviral Activity. Viruses 2016, 8, 158.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top