Reprogramming Viral Host Specificity To Control Insect Populations

One of the most diverse and successful group of animals, Insects are an integral part of ecosystems. Yet, some represent great nuisances for Human’s health and development...Such pests have been efficiently controlled using chemical insecticides, but the rise of resistances, the broadly untargeted environmental impacts and the increasing recognition of chronic toxicity call for the urgent development of safer and cleaner alternatives.Biological control strategies that take advantage of natural antogonistic relationships between existing organisms and a target pest have been around for millenia. In spite of the inherent risks of unintended side effects, these approaches have recently gained renewed interest.Perhaps because they evoke greater fears, surpisingly few microorganisms have been used in that perspective.Densoviruses are small viruses capable—as a group—of infecting a broad range of insects with various degree of specificity.Their minute genomes comprise a handful of genes, which lend themselves to in-depth molecular dissection using synthetic biology approaches.Our goal is to develop the tools and knowledge necessary to enable the use of densoviruses as safe, specific and efficient biocontrol agents. We focus on JcDV, which infects crop-devasting caterpillars and AalDV, which infects disease-vector mosquitoes.Here, I present early efforts to systematically unravel the structural motifs responsible for capsid specificity.The capsid of densoviruses are small (19-24 nm) non-enveloped icosahedrons (T=1) resulting from the self-assembly of 60 identical or highly similar capsid proteins. The DNA sequences coding these proteins represent roughly a third of the genome and are the prime determinant of specificity. I am using the genome of JcDV to setup a the high-throughput, cost-effective pipeline to deconstruct the phenotypic consequences of many precise capsid mutations. This will permit to better understand natural variations, to map evolutionary landscape, to discover uselful properties and to learn the rules to reprogram specificities.