Present address: Biomedical Research Laboratories, Takeda Pharmaceutical Company Limited, 2-17-85, Jusohonmachi, Yodgawa-ku, Osaka 532-8686, Japan.
Griffithsin, a potent HIV entry inhibitor, is an excellent candidate for anti-HIV microbicide
Article first published online: 1 AUG 2007
Journal of Medical Primatology
Volume 36, Issue 4-5, pages 244–253, August 2007
How to Cite
Emau, P., Tian, B., O’keefe, B.R., Mori, T., McMahon, J.B., Palmer, K.E., Jiang, Y., Bekele, G. and Tsai, C.C. (2007), Griffithsin, a potent HIV entry inhibitor, is an excellent candidate for anti-HIV microbicide. Journal of Medical Primatology, 36: 244–253. doi: 10.1111/j.1600-0684.2007.00242.x
- Issue published online: 1 AUG 2007
- Article first published online: 1 AUG 2007
- Accepted May 3, 2007.
- anti-HIV microbicide candidate;
- entry inhibitor of HIV;
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.