Transgenic plant production of Cyanovirin-N, an HIV microbicide

FASEB J. 2006 Feb;20(2):356-8. doi: 10.1096/fj.05-4742fje. Epub 2005 Dec 14.

Abstract

Cyanovirin-N (CV-N) is a microbicide candidate that inactivates a wide range of HIV strains by binding to gp120. Production of CV-N, or any protein microbicide, needs to be at extremely high levels and low cost to have an impact on global health. Thus, it is unlikely that fermentor-based systems will be suitable, including recombinant E. coli, where CV-N aggregates and dimers have consistently been found. Transgenic plants may provide a suitable expression system for protein microbicides, as production can be easily and economically scaled up. Here, Nicotiana tabacum was transformed with a gene encoding CV-N to explore proof of concept for the production of CV-N in transgenic plants. Plant-derived rCV-N was recoverable at levels of 130 ng/mg of fresh leaf tissue, or at least 0.85% of total soluble plant protein. Western blot analysis demonstrated that virtually all of the rCV-N was expressed in the desired monomeric form. Functionality was demonstrated by specific binding to gp120 and protection of T-cells from in vitro HIV infection. Hydroponic culturing of transgenic plants demonstrated CV-N rhizosecretion at levels of 0.64 mug/ml hydroponic media after 24 days. Therefore, we suggest that transgenic plants have the potential to provide strategies for large-scale protein microbicide production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / metabolism*
  • Bacterial Proteins / biosynthesis*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Carrier Proteins / biosynthesis*
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Gene Expression
  • HIV Envelope Protein gp120 / metabolism
  • Nicotiana / genetics*
  • Nicotiana / metabolism*
  • Plant Leaves / metabolism
  • Plants, Genetically Modified
  • Protein Binding

Substances

  • Anti-HIV Agents
  • Bacterial Proteins
  • Carrier Proteins
  • HIV Envelope Protein gp120
  • cyanovirin N