Deciphering the complex interactions between densoviruses and the insect gut – DECIDE
Densoviruses are orally infectious and lethal to insects of various orders. They are considered promising candidates, as an alternative to chemical insecticides, for the control of insect crop pests and disease vectors. Their use requires a prior in-depth understanding of viral pathogenesis and the mechanisms of their specificity. As with all orally infectious viruses, the key step that determines the initiation and success of host infection is the crossing of the intestinal barrier, although the mechanisms involved remain poorly understood. For most insects, this barrier consists of a peritrophic matrix and a monolayer epithelium, which it protects. This peritrophic matrix consists of a network of chitin fibrils associated with highly glycosylated proteins called peritrophins. The intestinal epithelium is covered by a layer of glycans, called glycocalyx, and the epithelial cells are joined by so-called "septate" junctions that ensure the impermeability of the tissue. In insect pests, the fine structure and extensive biochemical composition of the components of the intestinal barrier are not characterized, and to date, no densovirus receptors are known. The DECIDE project aims to decipher the specific molecular mechanisms used by densoviruses to cross the intestinal barrier in insects. We hypothesize that viral particles cross this barrier in two steps, first by interacting with certain glycans in the peritrophic matrix and/or intestinal epithelium, and then by accessing more specific membrane receptors that allow them to infect intestinal cells and invade the body. To test this two-step infection hypothesis, we will use as interaction models a densovirus type, the densovirus Junonia coenia (JcDV) and crop pests belonging to the genus Spodoptera (S. frugiperda and S. littoralis). Densovirus-intestinal interactions will also be evaluated in non-target species, Bombyx mori and Vanessa cardui. This project will decipher the mechanisms of interaction of the virus with the peritrophic matrix and intestinal epithelium and the consequences of these interactions on intestinal physiology. This project has four main objectives: i) To perform a complete analysis of the glycan and protein composition of the peritrophic matrix and the brush border of the intestinal epithelium; ii) To identify, among these, the glycans and/or proteins that interact with the viral particles and allow them to cross the intestinal barrier as well as a precise dissection of the capsid to identify the residues involved in these interactions; iii) Analysing the potential enzymatic activity of the capsid allowing it to cross the peritrophic matrix, as well as the molecular mechanisms leading to the increase in intestinal permeability following oral infection. Finally, iv) this project will explore a "capsid strategy" based on "natural" or synthetic pseudo-particles (VLPs) as biocontrol tools. This project will address virology, insect gut physiology, cellular biology and glycobiology issues in lepidopteran pest models, combining a wide range of methods including mainly glycomic, proteomic, high resolution imaging and synthetic biology approaches. This original project provides a conceptual and experimental framework to study the impact of the use of entomopathogenic agents in biological control of insect pests or vectors. It could lead to the development of new strategies, based on the use of densoviruses, that specifically target the gut of insects.
Madame Anne-Sophie Gosselin Grenet (Diversité, Génomes et Interactions Microorganismes-Insectes)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
DGIMI Diversité, Génomes et Interactions Microorganismes-Insectes
CBS Centre de biochimie structurale
University of Milan / Department of Biosciences
UGSF UMR 8576 - Unité de glycobiologie structurale et fonctionnelle
CBS Centre de biochimie structurale
Help of the ANR 553,213 euros
Beginning and duration of the scientific project: December 2021 - 48 Months