Griffithsin, a potent HIV entry inhibitor, is an excellent candidate for anti-HIV microbicide.
BACKGROUND
The predominant mode of HIV-1 transmission is by heterosexual contact. The cervical/vaginal mucosa is the main port of HIV entry in women. A safe and effective topical microbicide against HIV is urgently needed to prevent sexual transmission. Hence, we evaluated griffithsin (GRFT), a 12.7 kDa carbohydrate-binding protein, both native and recombinant GRFT, potently inhibited both CXCR4-and CCR5-tropic HIV infection and transmission in vitro.


METHODS
The antiviral efficacy of native and recombinant GRFT against CXCR4-and CCR5-tropic HIV and SHIV strains and SIVmac251 was evaluated by in vitro assays. We also evaluated the time course of antiviral activity and stability of GRFT in cervical/vaginal lavage as a function of pH 4-8.


RESULTS
Griffithsin blocked CXCR4-and CCR5-tropic viruses at less than 1 nm concentrations and exhibited a high potency. GRFT was stable in cervical/vaginal lavage fluid and maintained a similar potency of anti-HIV activity. GRFT is not only a highly potent HIV entry inhibitor, but also prevents cell fusion and cell-to-cell transmission of HIV.


CONCLUSIONS
The in vitro efficacy of GRFT revealed low cytotoxicity, high potency, rapid onset of antiviral activity and long-term stability in cervical/vaginal lavage. GRFT is an excellent candidate for anti-HIV microbicide development.
Washington National Primate Research Center, University of Washington, Seattle, WA 98195, USA.
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Emau
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Tian
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O'keefe
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Mori
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McMahon
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Palmer
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Jiang
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Bekele
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Tsai
D020418:Algal Proteins / Q000494:pharmacology*; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D037102:Lectins / Q000494:pharmacology*; D008254:Macaca nemestrina; D037121:Plant Lectins; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000378:metabolism / Q000502:physiology*; D044364:Vaginal Douching
D020418:Algal Proteins; D019380:Anti-HIV Agents; D037102:Lectins; D037121:Plant Lectins; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; C499654:griffithsin protein, Griffithsia