Biological and biochemical characterization of HIV-1 Gag/dgp41 virus-like particles expressed in Nicotiana benthamiana

Plant Biotechnol J. 2013 Aug;11(6):681-90. doi: 10.1111/pbi.12058. Epub 2013 Mar 19.

Abstract

The transmembrane HIV-1 envelope protein gp41 has been shown to play critical roles in the viral mucosal transmission and infection of CD4⁺ cells. Gag is a structural protein configuring the enveloped viral particles and has been suggested to constitute a target of the cellular immunity that may control viral load. We hypothesized that HIV enveloped virus-like particles (VLPs) consisting of Gag and a deconstructed form of gp41 comprising the membrane proximal external, transmembrane and cytoplasmic domains (dgp41) could be expressed in plants. To this end, plant-optimized HIV-1 genes were constructed and expressed in Nicotiana benthamiana by stable transformation, or transiently using a Tobamovirus-based expression system or a combination of both. Our results of biophysical, biochemical and electron microscopy characterization demonstrates that plant cells could support not only the formation of enveloped HIV-1 Gag VLPs, but also the accumulation of VLPs that incorporated dgp41. These findings provide further impetus for the journey towards a broadly efficacious and inexpensive subunit vaccine against HIV-1.

Keywords: Gag; HIV-1; enveloped virus-like particles; gp41; transgenic plants; transient expression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Gene Expression Regulation, Plant
  • Genes, Synthetic
  • HIV Envelope Protein gp41 / metabolism*
  • HIV-1 / metabolism*
  • Nicotiana / genetics
  • Nicotiana / virology*
  • Plant Leaves / ultrastructure
  • Plant Leaves / virology
  • Plants, Genetically Modified
  • Virion / ultrastructure
  • gag Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • HIV Envelope Protein gp41
  • gag Gene Products, Human Immunodeficiency Virus
  • gp41 protein, Human immunodeficiency virus 1