Thursday, 5 December 2013

The fascinating biology of baculoviruses

Principles of Molecular Virology Principles of Molecular Virology, Chapter 2 (Virus Particles), discusses baculoviruses as examples of large and complex virus structures. But there's more to the fascinating biology of baculoviruses than the virus particle.

The baculoviruses (family: Baculoviridae) are a group of large DNA viruses that infect insects. Interest in baculoviruses as gene expression vectors took off in the 1990s and has remained constant since then (Baculovirus as versatile vectors for protein expression in insect and mammalian cells. (2005) Nature biotechnology, 23(5), 567-575):

Data from PubMed
Data from PubMed

Baculovirus nucleocapsids are rod-shaped and surrounded by an envelope, and contain circular genomes of double-stranded DNA that range in size from about 80–180 kbp in length. An unusual feature of these viruses is that they produce two distinct types of particle: occlusion-derived virions embedded in large (5–10 micron) protein crystals called occlusion bodies which are responsible for horizontal transmission between insects, and budded virions which spread infection from cell to cell. Baculoviruses are also the only known nuclear-replicating DNA viruses that encode a DNA-directed RNA polymerase, which is used to transcribe the virus late (structural) genes, and is also used to express foreign genes in the baculovirus expression vector system.

Figure 2.15: Baculovirus infection
Figure 2.15: Baculovirus Infection

The reason these viruses are so useful as expression vectors is because they are designed to produce massive amounts of a protein, polyhedrin, which has two functions. Firstly, it forms an outer protective crystalline occlusion body around the virus particle, allowing the virus to remain viable for many years outside the insect host until another host ingests it. Second, polyhedrin resists solubilization except under strongly alkaline conditions found in the insect midgut, thus delivering the virus through the insect stomach to the host target tissue. Substitute a gene of interest for the virus polyhedrin gene and massive qualities of recombinant protein can be produced.

Baculoviruses can also be used as insecticides although their use for insect control has been limited due to their relatively slow speed of kill, limited host range and the complexity of producing them. For these reasons, use of Bacillus thuringiensis as an insecticide is more common compared to baculoviruses because of the simplicity of production.

Although we have learned a lot about baculoviruses in the last few decades there is still much to find out. For example, baculovirus infection frequently alters the behaviour of the insect host, inducing climbing behaviour. This evolutionary adaptation is thought to aid in virus dispersal after death of infected insect larvae, resulting in increased dispersal of occluded virus particles. How exactly does the virus do this? Such changes are the result of the virus manipulating insect hormones, but there is still much to learn about the interactions of these complex viruses with their hosts. Half of the genes have no assigned function, meaning that there are probably many more interesting baculovirus genes whose functions are waiting to be discovered.

Further Reading:

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