Griffithsin, a potent HIV entry inhibitor, is an excellent candidate for anti-HIV microbicide.

Abstract

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.

• Authors: P Emau, B Tian, B R O'keefe, T Mori, J B McMahon, K E Palmer, Y Jiang, G Bekele, C C Tsai
• Journal: Journal of medical primatology (J Med Primatol) Vol. 36 Issue 4-5 Pg. 244-53 (Aug 2007) ISSN: 0047-2565 [Print] Denmark
• PMID: 17669213 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)

Chemical References

• Algal Proteins
• Anti-HIV Agents
• Lectins
• Plant Lectins
• Receptors, CCR5
• Receptors, CXCR4
• griffithsin protein, Griffithsia

Topics

• Algal Proteins (pharmacology)
• Animals
• Anti-HIV Agents (pharmacology)
• Cell Line
• Cell Survival (drug effects)
• Disease Models, Animal
• Female
• HIV Infections (immunology, prevention & control, virology)
• Humans
• Hydrogen-Ion Concentration
• Kinetics
• Lectins (pharmacology)
• Macaca nemestrina
• Plant Lectins
• Receptors, CCR5 (metabolism)
• Receptors, CXCR4 (metabolism)
• Simian Acquired Immunodeficiency Syndrome (immunology, prevention & control, virology)
• Simian Immunodeficiency Virus (metabolism, physiology)
• Vaginal Douching