Investigation of griffithsin's interactions with human cells confirms its outstanding safety and efficacy profile as a microbicide candidate.
Many natural product-derived lectins such as the red algal lectin griffithsin (GRFT) have potent in vitro activity against viruses that display dense clusters of oligomannose N-linked glycans (NLG) on their surface envelope glycoproteins. However, since oligomannose NLG are also found on some host p...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3149051?pdf=render |
| _version_ | 1818197717388623872 |
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| author | Joseph Calvin Kouokam Dana Huskens Dominique Schols Andrew Johannemann Shonna K Riedell Wendye Walter Janice M Walker Nobuyuki Matoba Barry R O'Keefe Kenneth E Palmer |
| author_facet | Joseph Calvin Kouokam Dana Huskens Dominique Schols Andrew Johannemann Shonna K Riedell Wendye Walter Janice M Walker Nobuyuki Matoba Barry R O'Keefe Kenneth E Palmer |
| author_sort | Joseph Calvin Kouokam |
| collection | DOAJ |
| description | Many natural product-derived lectins such as the red algal lectin griffithsin (GRFT) have potent in vitro activity against viruses that display dense clusters of oligomannose N-linked glycans (NLG) on their surface envelope glycoproteins. However, since oligomannose NLG are also found on some host proteins it is possible that treatment with antiviral lectins may trigger undesirable side effects. For other antiviral lectins such as concanavalin A, banana lectin and cyanovirin-N (CV-N), interactions between the lectin and as yet undescribed cellular moieties have been reported to induce undesirable side effects including secretion of inflammatory cytokines and activation of host T-cells. We show that GRFT, unlike CV-N, binds the surface of human epithelial and peripheral blood mononuclear cells (PBMC) through an exclusively oligosaccharide-dependent interaction. In contrast to several other antiviral lectins however, GRFT treatment induces only minimal changes in secretion of inflammatory cytokines and chemokines by epithelial cells or human PBMC, has no measureable effect on cell viability and does not significantly upregulate markers of T-cell activation. In addition, GRFT appears to retain antiviral activity once bound to the surface of PBMC. Finally, RNA microarray studies show that, while CV-N and ConA regulate expression of a multitude of cellular genes, GRFT treatment effects only minimal alterations in the gene expression profile of a human ectocervical cell line. These studies indicate that GRFT has an outstanding safety profile with little evidence of induced toxicity, T-cell activation or deleterious immunological consequence, unique attributes for a natural product-derived lectin. |
| first_indexed | 2024-12-12T01:54:25Z |
| format | Article |
| id | doaj.art-2a0e073c65784591a6d9b8f842dcacc4 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T01:54:25Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2a0e073c65784591a6d9b8f842dcacc42022-12-22T00:42:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0168e2263510.1371/journal.pone.0022635Investigation of griffithsin's interactions with human cells confirms its outstanding safety and efficacy profile as a microbicide candidate.Joseph Calvin KouokamDana HuskensDominique ScholsAndrew JohannemannShonna K RiedellWendye WalterJanice M WalkerNobuyuki MatobaBarry R O'KeefeKenneth E PalmerMany natural product-derived lectins such as the red algal lectin griffithsin (GRFT) have potent in vitro activity against viruses that display dense clusters of oligomannose N-linked glycans (NLG) on their surface envelope glycoproteins. However, since oligomannose NLG are also found on some host proteins it is possible that treatment with antiviral lectins may trigger undesirable side effects. For other antiviral lectins such as concanavalin A, banana lectin and cyanovirin-N (CV-N), interactions between the lectin and as yet undescribed cellular moieties have been reported to induce undesirable side effects including secretion of inflammatory cytokines and activation of host T-cells. We show that GRFT, unlike CV-N, binds the surface of human epithelial and peripheral blood mononuclear cells (PBMC) through an exclusively oligosaccharide-dependent interaction. In contrast to several other antiviral lectins however, GRFT treatment induces only minimal changes in secretion of inflammatory cytokines and chemokines by epithelial cells or human PBMC, has no measureable effect on cell viability and does not significantly upregulate markers of T-cell activation. In addition, GRFT appears to retain antiviral activity once bound to the surface of PBMC. Finally, RNA microarray studies show that, while CV-N and ConA regulate expression of a multitude of cellular genes, GRFT treatment effects only minimal alterations in the gene expression profile of a human ectocervical cell line. These studies indicate that GRFT has an outstanding safety profile with little evidence of induced toxicity, T-cell activation or deleterious immunological consequence, unique attributes for a natural product-derived lectin.http://europepmc.org/articles/PMC3149051?pdf=render |
| spellingShingle | Joseph Calvin Kouokam Dana Huskens Dominique Schols Andrew Johannemann Shonna K Riedell Wendye Walter Janice M Walker Nobuyuki Matoba Barry R O'Keefe Kenneth E Palmer Investigation of griffithsin's interactions with human cells confirms its outstanding safety and efficacy profile as a microbicide candidate. PLoS ONE |
| title | Investigation of griffithsin's interactions with human cells confirms its outstanding safety and efficacy profile as a microbicide candidate. |
| title_full | Investigation of griffithsin's interactions with human cells confirms its outstanding safety and efficacy profile as a microbicide candidate. |
| title_fullStr | Investigation of griffithsin's interactions with human cells confirms its outstanding safety and efficacy profile as a microbicide candidate. |
| title_full_unstemmed | Investigation of griffithsin's interactions with human cells confirms its outstanding safety and efficacy profile as a microbicide candidate. |
| title_short | Investigation of griffithsin's interactions with human cells confirms its outstanding safety and efficacy profile as a microbicide candidate. |
| title_sort | investigation of griffithsin s interactions with human cells confirms its outstanding safety and efficacy profile as a microbicide candidate |
| url | http://europepmc.org/articles/PMC3149051?pdf=render |
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