Baculovirus-Derived Vectors for Immunization and Therapeutic Applications

Abstract

Baculoviruses are insect-specific pathogens that have been isolated from about 600 species belonging to the orders Lepidoptera, Hymenoptera, Diptera, Orthoptera, Coleoptera, Neuroptera, Thysaneura, and Trichoptera. Taxonomy of Baculoviridae family includes four genera: Alphabaculovirus (nucleopolyhedroviruses specific of lepidopterans), Betabaculovirus (granuloviruses specific of lepidopterans), Gammabaculovirus (nucleopolyhedroviruses specific of hymenopterans), and Deltabaculovirus (granuloviruses specific of dipterans) (Jehle et al., 2006; Herniou et al., 2011). These viruses infect arthropod larvae and possess circular doublestranded deoxyribonucleic acid (DNA) genomes that range in size from 80 to 180 kbp. The baculoviral genome is packed inside a distinct rod-shaped nucleocapsid (NC). The life cycle of baculoviruses is biphasic, and each phase is characterized by a different viral phenotype. In the environment, baculoviruses are found as occlusion bodies (OBs). A protein matrix encloses virions and provides protection against harsh environmental conditions such as temperature, dehydration, and ultraviolet light until a susceptible larva ingests the OBs. Briefly, the baculovirus infection cycle of insect hosts is as it follows: OBs are ingested together with foliage by larvae and dissolved in the midgut-releasing occlusion-derived viruses (ODVs), and the damaged peritrophic membrane allows the receptormediated endocytosis of the ODV by epithelial cells (Adams and McClintock., 1991). ODVs may contain one or multiple rod-shaped NCs depending on the baculovirus (or less frequently on growth conditions). The NCs enter the cytoplasm and translocate to the nucleus where the viral DNA is transcribed and replicated. Newly synthesized genomic DNA assembles with specific viral proteins to form the NCs in the nucleus. The NCs travel to the plasma membrane where budding takes place to yield the budded viruses (BVs), the second viral phenotype, responsible for the systemic infection of the larvae.