Cost-Effective Production of HIV Entry Inhibitor, Griffithsin


Topical application of viral entry inhibitors or other microbicides is an attractive strategy to prevent sexual transmission of the human immunodeficiency virus (HIV). Griffithsin, a protein isolated from the red algae Griffithsia sp which grows off the coast of New Zealand, has been shown in vitro to be a potent HIV entry inhibitor, but the cost of production has so far hampered its development.

Nicotiana benthamianaWriting in the March 30th Early Edition of PNAS, a multinational team of scientists has now described a breakthrough which should allow the manufacture and isolation of significant amounts of griffithsin as an agricultural crop. Griffithsin was shown to accumulate to a level of more than 1 gram of recombinant protein per kilogram of leaf material of Nicotiana benthamiana when expressed via an infectious tobacco mosaic virus vector. Nicotiana benthamiana, which is native to Australia, is a close relative of the tobacco plant and the authors were able to produce more than 60g of pure griffithsin from a single greenhouse with an area of 5000 square feet. The biophysical characteristics of griffithsin and the nature of the plant host allowed isolation of 99% pure protein after a simple 3-step purification procedure.

The plant-produced protein was found to have broad and potent activity against a panel of primary sexually transmitted HIV-1 isolates representative of viruses prevalent in sub-Saharan Africa, Asia and the West. The recombinant griffithsin was further shown to be non-irritating and non-inflammatory, and to have no mitogenic activity. Since viral entry inhibitors are not commonly used in resource-poor countries, griffithsin produced cost-effectively in Nicotiana benthamiana plants has the potential for prevention and treatment of multi-drug resistant viral infections in developing countries.

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