Cyanovirin-N produced in rice endosperm offers effective pre-exposure prophylaxis against HIV-1BaL infection in vitro

Plant Cell Rep. 2016 Jun;35(6):1309-19. doi: 10.1007/s00299-016-1963-5. Epub 2016 Mar 23.

Abstract

Cyanovirin-N produced in rice endosperm provides efficient pre-exposure prophylaxis against HIV-1 BaL infection in vitro. Cyanovirin-N (CV-N) is a lectin with potent antiviral activity that has been proposed as a component of microbicides for the prevention of infection with Human immunodeficiency virus (HIV). The production of protein-based microbicide components requires a platform that is sufficiently economical and scalable to meet the demands of the large at-risk population, particularly in resource poor developing countries. We, therefore, expressed CV-N in rice endosperm, because the dried seed is ideal for storage and transport and crude extracts could be prepared locally and used as a microbicide component without further purification. We found that crude extracts from rice seeds expressing up to 10 µg CV-N per gram dry seed weight showed dose-dependent gp120 binding activity, confirming that the protein was soluble, correctly folded and active. The recombinant lectin ((OS)CV-N) reduced the infectivity of HIV-1BaL (an R5 virus strain representing the majority of transmitted infections) by ~90 % but showed only weak neutralization activity against HIV-1RF (representative of X4 virus, rarely associated with transmission), suggesting it would be highly effective for pre-exposure prophylaxis against the vast majority of transmitted strains. Crude extracts expressing (OS)CV-N showed no toxicity towards human cells at working dilutions indicating that microbicide components produced in rice endosperm are safe for direct application as topical microbicides in humans.

Keywords: Anti-HIV; Cyanovirin-N; Endosperm; Microbicide; Rice crude extract.

MeSH terms

  • Bacterial Proteins / metabolism
  • Bacterial Proteins / therapeutic use*
  • Carrier Proteins / metabolism
  • Carrier Proteins / therapeutic use*
  • Dose-Response Relationship, Drug
  • Endosperm / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • HIV Infections / prevention & control*
  • HIV-1 / drug effects*
  • HeLa Cells
  • Humans
  • In Vitro Techniques
  • Neutralization Tests
  • Oryza / metabolism*
  • Phytotherapy / methods
  • Plant Extracts / therapeutic use*
  • Plants, Genetically Modified
  • Pre-Exposure Prophylaxis / methods*

Substances

  • Bacterial Proteins
  • Carrier Proteins
  • Plant Extracts
  • cyanovirin N