Biology and Biotechnology of Baculoviruses

The insect viruses studied in our Laboratory are the baculoviruses, which cause fatal diseases in insects. For this reason they have great potential for the biocontrol of pest insects (Lepidopteran and Hymenopteran) in agriculture and forestry thereby replacing chemical insecticides.

The Insect Virus Group

BSc and MSc students

A varying number of BSc and MSc students (Biology, Biotechnology, Molecular Sciences, animal Sciences) participates in the ongoing research. Students can participate for their thesis in the above mentioned research projects. Students are also encouraged to perform an internship in virology, through the many international contacts that we have.

Requirements:

BSc: Cell Biology and Health (CBI-20806)

MSc: Molecular virology (VIR30306) or Fundamental and Applied Virology VIR30806) is required. Immuntechnology is recommended (CBI-30806).

Technical skills that can be developed: Recombinant DNA techniques, insect cell culturing, virus handling and titration methods, infectivity tests in insects (bioassays), baculovirus/insect cell system for expression of heterologous proteins, (RT-)PCR, QT-PCR, immunological techniques, EM and confocal laser microscopy, RNA/DNA transfections, quantitative gene expression assays (luciferase luminometry), infections of insects and behavioral studies.

Current research themes

The current research projects in the insect virus group are divided over four main categories:

  1. Functional genomics and biodiversity of insect viruses
  2. Baculoviruses, host behavior
  3. UV sensitivity of baculoviruses
  4. Baculovirus/insect cell technology for the development of vaccines and gene therapy vectors
Fig.1 Baculovirus phenotypes (Van Oers and Vlak (2007), Current Drug Targets 8, 1051-68)
Fig.1 Baculovirus phenotypes (Van Oers and Vlak (2007), Current Drug Targets 8, 1051-68)

1. Functional genomics of insect viruses

Projects in this category concentrate on the functional genomics of baculoviruses and insect iridoviruses. Special attention is given to entry mechanisms of baculoviruses into gut and insect body cells (PhD student Qiushi Wang), determination of structural proteins of iridoviruses (PhD student Agah Ince). Baculoviruses have so called per os infectivity factors that are crucial for oral infection in larvae. Current studies focus on the function of these four proteins and their possible interactions (PhD student Ke Peng).

2.  Baculoviruses and host behavior

This project concentrates on behavioural changes of insects after virus infections. Behavioural changes of insects associated with baculovirus infection secure optimal dissemination of progeny virus in the environment. Infected insects show a radical change in behaviour as they become hypermobile and they move towards the canopy of plants or trees. There they die from the virus infection and ‘spray’ the progeny virus over the foliage, thereby increasing the chance of establishing a new round of infection in other insects. The central hypothesis of this project is that baculoviruses, besides known genes for virus replication and virion structure, contain genes to modulate their host, including genes that alter host behaviour. The aims are (i) to identify the viral genes responsible for altered insect behaviour (PhD student) and (ii) to unravel the pathways that transduce the virus-encoded signal in the insect and explain the changes in behaviour (PhD student Stineke van Houte and post-doc Vera Ros).

3. UV sensitivity of baculoviruses

The moving towards the canopy exposes both the infected insects and the progeny virus to enhanced doses of sunlight and a trade-off is expected between optimal virus dissemination and inactivation by ultraviolet light (UV). In parallel, the function of recently discovered DNA photolyase genes will be analyzed. Photolyases have a potential function in repairing DNA lesions induced by UV light and the question is whether these genes provide a solution against UV exposure. With the proposed coupling of genes and behaviour a new research area will be explored to understand baculovirus ecology (PhD students Xu Fang and Magda Biernat).

    Fig.2 Interaction of baculovirus DNA photolyase with cellular chromosomes       (Xu et al (2010), JGV 91, 907 – 914)
Fig.2 Interaction of baculovirus DNA photolyase with cellular chromosomes (Xu et al (2010), JGV 91, 907 – 914)

4. Baculovirus/insect cell technology for the development of vaccines and gene therapy vectors

The main goal of this theme is to improve the existing baculovirus vectors for vaccine production and gene therapy. Optimization is sought in increasing genome stability, improving the quality of the expressed (glycol) proteins and reducing genome content. For the gene therapy part we collaborate for human genetic diseases and cancer treatment with partners in the EU.

Collaborations

We are part of an European consortium aimed at exploiting baculoviruses for gene therapy in the project BACULOGENES. We form a Chinese-Dutch consortium with the the Institute for Virology in Wuhan, South China Normal University in Guangzhou and Tsinghua University in Beijing, The Laboratory of Veterinary Virology, and the Laboratory of Biochemistry, both at Utrecht University (NL). This consortium focuses on entry, transport and virus escape mechanisms in insect cells financed by the Royal Dutch Academy of Science (KNAW). In addition we collaborate with many other laboratoria, including the Cell Biology and Genetics Laboratory, Erasmus University (NL), Intervet International in Boxmeer (NL) and Penn State University.

Publications in peer reviewed journals