EM of baculovirus infected insect cells
EM of baculovirus infected insect cells

Project keywords

Systems Biology, Systems Biotechnology, Sustainability, Fermentation, Baculovirus, Biopesticide

Project summary

Many of the most significant pests of agriculture and forestry, and vectors of human disease, have developed resistance to multiple conventional chemical insecticides; six species now account for more than US$5 billion worth of chemical insecticides (see Table 1). At the same time, pesticides based on new chemistries has become harder and more costly to develop, register and commercialise. "Wild-Type" Baculoviruses are one of the most promising biocontrol options for insect pests resistant to chemical insecticides, since the hosts are rarely able to develop resistance. However, conventional production in insectaries do not offer the necessary scale benefit to compete with selective chemicals.

We are developing an in vitro (within bioreactors) production process that can produce large quantities of Baculovirus Biopesticides at costs comparable to selective chemicals (i.e. $20/Ha). It has the potential to transform agriculture, allowing farmers to choose an insect control option that is safe and efficacious to use, as well as economically and environmentally superior to chemicals. The project combines conventional biochemical engineering R&D with a systems biology approach to identify process parameters as well as cell line gene targets for yield improvements.

Table 1: Economically important insect pests (Crop Protection Compendium 2006)1
Insect pests Infected regions Effect Pesticides (US$/year)
Helicoverpa Complex:(armigera, zea,virescens, assulta) Africa, Asia- Pacific, Europe, Middle East, North and South America Maize, sorghum, soybean, cotton, sunflower, pulses, hort., tobacco, $1.7 Billion
Diamondback moth (Plutella xylostella) Africa, Asia- Pacific, Europe, Middle East, North and South America crucifers, particularly cabbages, broccoli and cauliflowers $1 Billion
Spodoptera Species (exigua,frugiperda, littoralis, litura) Asia, Middle East, North and South America cotton, soybeans, sugar beet, lucerne, maize $800 Million
Culex culex mosquitos (C.nigripalpus, C.tarsalis etc) Temperate regions of Europe and North America Encephalitis &. West Nile River Virus > 7,000 cases in US in 2003 $700 Million
Codling Moth (Cydia pomonella) Australia, Europe, Central and South America pome fruit (i.e. apple, pear) $500 Million
Velvetbean Caterpillar (Anticarsia gemmatalis) Central and South America beans (e.g. soybean) $350 Million

1 Crop Protection Compendium. 2006. Reports on Helicoverpa, Spodoptera, Plutella, Cydia, Anticarsia and Culex. http://www.cabicompendium.org/cpc/datasheet.asp?CCODE=HELIAR&COUNTRY=0. Accessed 2007 April 21.



Huynh HT, Tran TT, Chan LC, Nielsen LK, Reid S (2015) Decline in Helicoverpa armigera nucleopolyhedrovirus occlusion body yields with increasing infection cell density in vitro is strongly correlated with viral DNA levels. Arch Virol 160: 2169-80. PMID: 26092423

Huynh HT, Tran TT, Chan LC, Nielsen LK, Reid S (2015) Effect of the peak cell density of recombinant AcMNPV-infected Hi5 cells on baculovirus yields. Appl Microbiol Biotechnol 99:1687-1700. PMID: 25472440

Matindoost L, Hu H, Chan LC, Nielsen LK, Reid S (2014) The effect of cell line, phylogenetics and medium on baculovirus budded virus yield and quality. Arch Virol. 159: 91-102. PMID: 23884632

Nguyen Q, Nielsen LK, Reid S (2013) Genome Scale Transcriptomics of Baculovirus-Insect Interactions. Viruses 5: 2721-2747. PMID: 24226166. PMC3856412

Nguyen QH, Chan LCL, Nielsen LK, Reid S (2013) Genome scale analysis of differential mRNA expression of Helicoverpa zea insect cells infected with a H. armigera baculovirus. Virology 444: 158-170. PMID: 23827436

Huynh HT, Tran TTB, Chan LCL, Nielsen LK, Reid S  (2013) Decline in baculovirus-expressed recombinant protein production with increasing cell density is strongly correlated to impairment of virus replication and mRNA expression. Appl Microbiol Biotechnol 97:5245–5257. PMID: 23519736

Matindoost L, Chan LCL, Qi YM, Nielsen LK, Reid S (2012) Suspension culture titration: A simple method for measuring baculovirus titers. Journal of Virological Methods 183: 201–209. PMID: 22561639

Huynh HT, Chan LCL, Tran TTB, Nielsen LK, Reid S  (2012) Improving the robustness of a low-cost insect cell medium for baculovirus biopesticides production, via hydrolysate streamlining using a tube bioreactor-based statistical optimization routine. Biotechnology Prog 28: 788-802. PMID: 22323401

Nguyen QH, Palfreyman RW, Chan LCL, Reid S, Nielsen LK (2012) Transcriptome sequencing of and microarray development for a Helicoverpa zea cell line to investigate in vitro insect cell-baculovirus interactions. PloS ONE 7(5):e36324. PMID: 22629315. PMC3356360

Tran TTB, Dietmair S, Chan LCL, Huynh HT, Nielsen LK, Reid S (2012) Development of quenching and washing protocols for quantitative intracellular metabolite analysis of uninfected and baculovirus-infected insect cells. Methods 56: 396-407. PMID: 22166686

Nguyen Q, Qi YM, Wu Y, Chan LCL, Nielsen LK, Reid S (2011) In vitro production of Helicoverpa baculovirus biopesticides - Automated selection of insect cell clones for manufacturing and systems biology studies. J. Virol. Meth. 175: 197-205. PMID: 21616093.

Pedrini MRS, Reid S, Nielsen LK, Chan LCL (2010) Kinetic characterization of the Group II Helicoverpa armigera nucleopolyhedrovirus propagated in suspension cell cultures: implications for development of a biopesticides production process. Biotechnology Progress 27: 614-24. PMID: 21644255.

Chen LCL, Reid S, Nielsen LK (2010) Baculovirus virus kinetics in insect cell culture. In: Encyclopedia of Industrial Biotechnology: Bioprocess, Bioseparation, and Cell Technology, ed. MC Flickinger. John Wiley & Sons. ISBN: 978-0-471-79930-6. Publication date: March 2010. 

Pedrini MRD, Chan LCL, Nielsen LK, Reid S, (2006) In vitro production of Helicoverpa armigera single-nucleocapsid nucleopolyhedrovirus. Brazilian Archives of Biology and Technology 49: 35-41SI.

Pedrini MRD, Christian P, Nielsen LK, Reid S, Chan LCL (2006) Importance of virus-medium interactions on the biological activity of wild-type Heliothine nucleopolyhedroviruses propagated via suspension insect cell cultures. Journal of Virological Methods 136:267-272.

Haas R, Nielsen LK (2005) A Physiological Product-Release Model for Baculovirus Infected Insect Cells. Bioengineering & Biotechnology 91: 768-772.

Pedrini MRS, Nielsen LK, Reid S, Chan LCL (2005) Properties of a unique mutant of Helicoverpa armigera single-nucleocapsid nucleopolyhedrovirus that exhibits both Many Polyhedra and Few Polyhedra phenotypes upon extended serial passaging in cell cultures. In Vitro Cellular & Developmental Biology – Animal 41:289-297.

Project contacts

Lead investigator Dr Steve Reid, Professor Lars Nielsen
Research group AIBN Systems & Synthetic Biology
Contact email steven.reid@uq.edu.au



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