Baculovirus are virus that infect insects, they are very stable and may remain dormant in the environment for years before infecting insects. The virus can be purified and produced in quantity to be used in insect control. Since the virus multiplies and persists its use in pest control seems promising.

The virus alone has a relatively low killing power and slow action. When a gene for a potent toxin such as scorpion toxin or a gene effecting a juvenile hormone is added to the virus it kills faster and fewer insects survive infection. Numerous field tests of modified virus sprayed on crops have been undertaken often accompanied by loud expressions of concern from the public. Soon after GM virus were developed for insect control it was found that baculovirus were capable of infecting human liver cells and produced relatively little toxicity to the infected cells. For that reason baculovirus vectors were developed to treat liver disease.

Interestingly, the fact that baculovirus can infect human liver cells seems to have been ignored by those developing the virus for commercial pest control. The following discussion will deal with the use of baculovirus vectors and their safety. I understand that there has been a great deal of pressure to hasten approval of the GM baculovirus for pest control. Ecological considerations for the impact of recombinant baculovirus insecticides have been studied extensively (Richards et al 1998). The study emphasized baculovirus containing scorpion toxin because that construction has been most widely studied. Impact on non-target insects is extrapolated from insects of related phylogeny, a practice difficult to defend. The recombinant baculovirus were very persistent and capable of reshaping an ecosystem. Modification of baculovirus host range specificity has been achieved by inserting or deleting genes (Theim 1997). Baculovirus is a circular DNA duplex, it replicates in the insect cell nucleus and replication is prone to the generation of defective genomes by deletion (Wu et al 1999).

The mode of virus replication seems to make the recombinant virus highly unpredictable and prone to generating potentially undesirable variants. This important finding has not yet influenced the risk analysis of recombinant baculovirus insecticides and gene therapy vectors.

The scorpion toxins used with recombinant baculovirus have been selected to avoid human neurotoxicity and as much as possible toxicity to non-target animals. However, the allergenicity of toxins and their behavior ( as for example in autoimmunity) in human liver infection has not yet been studied. In insect control the depressant toxin was more effective than the excitatory toxin in recombinant baculovirus (Gershburg et al 1998).

Recombinant baculovirus containing Bacillus thuringiensis toxin have not proven successful in controlling insect pests (Martens et al 1995). However, recombinant baculovirus modifying juvenile hormone proved effective in insect control (Bonning et al 1999). Recombinant baculovirus containing an antisense fragment to the c-myc oncogene proved effective in target insect control (Lee et al 1997). The behavior of the myc oncogene recombinant vector bears careful study regarding non-target animals and its impact during human lliver infection.

Baculovirus vectors efficiently transfer genes into human liver cells (Hofmann et al 1995; Boyce and Bucher 1996). The vectors transferred into human liver tissues most effectively in perfused liver tissue because serum components hampered virus transfer (Sandig et al 1996).Human conditions causing defects in complement should allow liver transfer of recombinant baculovirus. Inhibitors of complement facilitate baculovirus gene transfer (Hofmann and Strauss 1998). Hybrid baculovirus-adeno virus vectors have been used to deliver genes to human cells (Palombo et al 1998). Baculovirus vectors have been used to deliver hepatitis B to human liver efficiently to allow study of hepatitis B drug therapy (Delaney et al 1999).

In conclusion baculovirus vectors are being used to control insect pests because they are effective and persist for a long time in the environment. Baculovirus vectors are also being used in gene therapy of human liver. These areas of research seem to exist as two solitudes and the risks of one are not evaluated in the context of the other. The most disconcerting finding is the one showing that replication of the baculovirus is inherently unpredictable. However, there may be some who believe that we should all have unlabelled liver gene therapy with our salad.

References

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