Studies in a Murine Model Confirm the Safety of Griffithsin and Advocate Its Further Development as a Microbicide Targeting HIV-1 and Other Enveloped Viruses
Griffithsin (GRFT), a lectin from Griffithsia species, inhibits human immunodeficiency virus-1 (HIV-1) replication at sub-nanomolar concentrations, with limited cellular toxicity. However, in vivo safety of GRFT is not fully understood, especially following parenteral administration. We first assess...
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| Format: | Article |
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MDPI AG
2016-11-01
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| Series: | Viruses |
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| Online Access: | http://www.mdpi.com/1999-4915/8/11/311 |
| _version_ | 1818137388365381632 |
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| author | Joseph Calvin Kouokam Amanda B. Lasnik Kenneth E. Palmer |
| author_facet | Joseph Calvin Kouokam Amanda B. Lasnik Kenneth E. Palmer |
| author_sort | Joseph Calvin Kouokam |
| collection | DOAJ |
| description | Griffithsin (GRFT), a lectin from Griffithsia species, inhibits human immunodeficiency virus-1 (HIV-1) replication at sub-nanomolar concentrations, with limited cellular toxicity. However, in vivo safety of GRFT is not fully understood, especially following parenteral administration. We first assessed GRFT’s effects in vitro, on mouse peripheral blood mononuclear cell (mPBMC) viability, mitogenicity, and activation using flow-cytometry, as well as cytokine secretion through enzyme-linked immunosorbent assay (ELISA). Toxicological properties of GRFT were determined after a single subcutaneous administration of 50 mg/kg or 14 daily doses of 10 mg/kg in BALB/c mice. In the context of microbicide development, toxicity of GRFT at 2 mg/kg was determined after subcutaneous, intravaginal, and intraperitoneal administrations, respectively. Interestingly, GRFT caused no significant cell death, mitogenicity, activation, or cytokine release in mPBMCs, validating the usefulness of a mouse model. An excellent safety profile for GRFT was obtained in vivo: no overt changes were observed in animal fitness, blood chemistry or CBC parameters. Following GRFT treatment, reversible splenomegaly was observed with activation of certain spleen B and T cells. However, spleen tissues were not pathologically altered by GRFT (either with a single high dose or chronic doses). Finally, no detectable toxicity was found after mucosal or systemic treatment with 2 mg/kg GRFT, which should be further developed as a microbicide for HIV prevention. |
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| format | Article |
| id | doaj.art-0d8044f793c249f7abe4c06808e011f0 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-11T09:55:30Z |
| publishDate | 2016-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-0d8044f793c249f7abe4c06808e011f02022-12-22T01:12:16ZengMDPI AGViruses1999-49152016-11-0181131110.3390/v8110311v8110311Studies in a Murine Model Confirm the Safety of Griffithsin and Advocate Its Further Development as a Microbicide Targeting HIV-1 and Other Enveloped VirusesJoseph Calvin Kouokam0Amanda B. Lasnik1Kenneth E. Palmer2Department of Pharmacology and Toxicology, University of Louisville School of Medicine, University of Louisville, Louisville, KY 40202, USAJames Graham Brown Cancer Center, University of Louisville School of Medicine, University of Louisville, Louisville, KY 40202, USADepartment of Pharmacology and Toxicology, University of Louisville School of Medicine, University of Louisville, Louisville, KY 40202, USAGriffithsin (GRFT), a lectin from Griffithsia species, inhibits human immunodeficiency virus-1 (HIV-1) replication at sub-nanomolar concentrations, with limited cellular toxicity. However, in vivo safety of GRFT is not fully understood, especially following parenteral administration. We first assessed GRFT’s effects in vitro, on mouse peripheral blood mononuclear cell (mPBMC) viability, mitogenicity, and activation using flow-cytometry, as well as cytokine secretion through enzyme-linked immunosorbent assay (ELISA). Toxicological properties of GRFT were determined after a single subcutaneous administration of 50 mg/kg or 14 daily doses of 10 mg/kg in BALB/c mice. In the context of microbicide development, toxicity of GRFT at 2 mg/kg was determined after subcutaneous, intravaginal, and intraperitoneal administrations, respectively. Interestingly, GRFT caused no significant cell death, mitogenicity, activation, or cytokine release in mPBMCs, validating the usefulness of a mouse model. An excellent safety profile for GRFT was obtained in vivo: no overt changes were observed in animal fitness, blood chemistry or CBC parameters. Following GRFT treatment, reversible splenomegaly was observed with activation of certain spleen B and T cells. However, spleen tissues were not pathologically altered by GRFT (either with a single high dose or chronic doses). Finally, no detectable toxicity was found after mucosal or systemic treatment with 2 mg/kg GRFT, which should be further developed as a microbicide for HIV prevention.http://www.mdpi.com/1999-4915/8/11/311GriffithsinHIVsafetymouse modelmicrobicideperipheral blood mononuclear cells (PBMCs) |
| spellingShingle | Joseph Calvin Kouokam Amanda B. Lasnik Kenneth E. Palmer Studies in a Murine Model Confirm the Safety of Griffithsin and Advocate Its Further Development as a Microbicide Targeting HIV-1 and Other Enveloped Viruses Viruses Griffithsin HIV safety mouse model microbicide peripheral blood mononuclear cells (PBMCs) |
| title | Studies in a Murine Model Confirm the Safety of Griffithsin and Advocate Its Further Development as a Microbicide Targeting HIV-1 and Other Enveloped Viruses |
| title_full | Studies in a Murine Model Confirm the Safety of Griffithsin and Advocate Its Further Development as a Microbicide Targeting HIV-1 and Other Enveloped Viruses |
| title_fullStr | Studies in a Murine Model Confirm the Safety of Griffithsin and Advocate Its Further Development as a Microbicide Targeting HIV-1 and Other Enveloped Viruses |
| title_full_unstemmed | Studies in a Murine Model Confirm the Safety of Griffithsin and Advocate Its Further Development as a Microbicide Targeting HIV-1 and Other Enveloped Viruses |
| title_short | Studies in a Murine Model Confirm the Safety of Griffithsin and Advocate Its Further Development as a Microbicide Targeting HIV-1 and Other Enveloped Viruses |
| title_sort | studies in a murine model confirm the safety of griffithsin and advocate its further development as a microbicide targeting hiv 1 and other enveloped viruses |
| topic | Griffithsin HIV safety mouse model microbicide peripheral blood mononuclear cells (PBMCs) |
| url | http://www.mdpi.com/1999-4915/8/11/311 |
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