Baculoviridae is a family of viruses. Arthropods, among the most studied being Lepidoptera, Hymenoptera and Diptera, serve as natural hosts. Currently, 85 species are placed in this family, assigned to four genera. Baculoviruses are known to infect insects, with over 600 host species having been described. Immature (larval) forms of lepidopteran species (moths and butterflies) are the most common hosts, but these viruses have also been found infecting sawflies, and mosquitoes. Although baculoviruses are capable of entering mammalian cells in culture, they are not known to be capable of replication in mammalian or other vertebrate animal cells. Starting in the 1940s, they were used and studied widely as biopesticides in crop fields. Baculoviruses contain a circular, double-stranded DNA (dsDNA) genome ranging from 80 to 180 kbp.
Historical influence The earliest records of baculoviruses can be found in the literature from as early as the 16th century in reports of "wilting disease" infecting silkworm larvae. Starting in the 1940s, the viruses were used and studied widely as biopesticides in crop fields. Since the 1990s, they have been employed to produce complex eukaryotic proteins in insect cell cultures (see Sf21, High Five cells). These recombinant proteins have been used in research and as vaccines in both human and veterinary medical treatments (for example, the most widely used vaccine for prevention of H5N1 avian influenza in chickens was produced in a baculovirus expression vector). More recently, baculoviruses were found to transduce mammalian cells with a suitable promoter.
Baculovirus lifecycle
The baculovirus lifecycle involves two distinct forms of virus. Occlusion-derived virus (ODV) is present in a protein matrix (polyhedrin or granulin) and is responsible for the primary infection of the host, while the budded virus (BV) is released from the infected host cells later during the secondary infection. Baculoviruses have very species-specific tropisms among the invertebrates with over 700 host species having been described. Immature (larval) forms of lepidopteran species are the most common hosts, but these viruses have also been found infecting sawflies and mosquitoes. Reports of baculovirus infections of shrimp and beetles (e.g. Oryctes rhinocerus) were found to be nudiviruses, a closely related lineage to the baculoviruses. Typically, the initial infection occurs when a susceptible host insect feeds on plants that are contaminated with the occluded form of the virus. The protein matrix dissolves in the alkaline environment of the host midgut (stomach), releasing ODVs that then fuse to the columnar epithelial cell membranes of the host intestine and are taken into the cell in endosomes. Nucleocapsids escape from the endosomes and are transported to nucleus. This step is possibly mediated by actin filaments. Viral transcription and replication occur in the cell nucleus and new BV particles are budded out from the basolateral side to spread the infection systemically. During budding, BV acquires a loosely fitting host cell membrane with expressed and displayed viral glycoproteins.
After baculovirus infection, three distinct phases occur:
Early (0–6 h), Late (6–24 h) Very late phase (18–24 to 72 h) While BV is produced in the late phase, the ODV form is produced in the very late phase, acquiring the envelope from host cell nucleus and embedded in the matrix of occlusion body protein. These occlusion bodies are released when cells lyse to further spread baculovirus infection to next host. The extensive lysis of cells frequently causes the host insect to literally disintegrate, thus the reason for the historic name "wilting disease". The complete ODV-polyhedrin particles are resistant to heat and light inactivation, whereas the naked BV virion is more sensitive to environment. When infecting a caterpillar, the advanced stages of infection cause the host to feed without resting, and then to climb to the higher parts of trees, including exposed places they would normally avoid due to the risk of predators. This is an advantage for the virus since (when the host dissolves) it can drip down onto leaves, which will be consumed by new hosts.
Transmissibility
The virus is unable to infect humans in the way it does insects, because human stomachs are acid-based and NPV requires an alkaline digestive system in order to replicate. It is possible for the virus crystals to enter human cells, but not to replicate to the point of causing illness.
Structure of the virion
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