A Review of Vip3A Mode of Action and Effects on Bt Cry Protein-Resistant Colonies of Lepidopteran Larvae

The ability to protect crops from agriculturally important larval pests was transformed with the introduction of transgenically enhanced cultivars of maize, Zea mays L., designed to express -endotoxins derived from Bacillus thuringiensis Berliner (Bt). Bt crystalline -endotoxins (Bt Cry proteins) protect crops by disrupting the insect midgut after ingestion, typically leading to feeding reduction or cessation and eventual death of susceptible insects. The mode of action of Bt Cry proteins involves activation by gut proteases after ingestion, binding to midgut receptors on the brush border membrane, and pore formation leading to cell lysis. The most common mechanism of resistance to Bt Cry proteins is reduced or altered binding to midgut receptors. The most direct method to delay or overcome resistance to a single Bt Cry protein is to pyramid in the same plant two or more genes expressing proteins that bind to independent receptors. While Bt Cry proteins and their effects on insects are the most widely studied, Bt also produces additional vegetative insecticidal proteins commonly known as Vips. Isolation of Vip3A from Bt was first reported by Ciba Agricultural Biotechnology (now Syngenta Biotechnology, Inc.) by Estruch et al. (1996). The discovery of Vip3A revealed a novel class of insecticidal proteins with activity against a range of agriculturally important lepidopteran larvae including black cutworm, Agrotis ipsilon (Hufnagel); fall armyworm, Spodoptera frugiperda (J. E. Smith); tobacco budworm, Heliothis virescens (Fabricius); and corn earworm, Helicoverpa zea (Boddie). Initially, the reported novelty of Vip3A was based on two key findings. First, Vip3A is an exotoxin produced and secreted without N-terminal processing during the vegetative growth stage of Bt. This differs from Bt Cry proteins produced during sporulation. Secondly, Vip3A shares no sequence homology with any known Bt Cry proteins. The amount of shared sequence homology between Bt Cry proteins is an important indicator of the risk that the two Bt Cry proteins will share binding sites on the midgut of the insect, predisposing the proteins to cross-resistance (Tabashnik 1994). The differences in production stage and lack of sequence homology with Bt Cry proteins were the first indicators that Vip3A would be an important new tool for transgenic control of lepidopteran pests and complement Bt Cry proteins in pyramided products for enhanced strategies to slow the development of resistance. To build on the initial indications, Syngenta Biotechnology, Inc. and others have further studied the mode of action and effects of Vip3A on insect strains resistant to Bt Cry proteins. Yu et al. (1997) described the first reported study of the mode of action of Vip3As. Their observations focused on the effect of Vip3A on the target cells of