Research Interests:

Viral DNA replication, analysis of essential virus genes and their regulation.

Members of the Baculoviridae, a unique family of eukaryotic of rod-shaped enveloped viruses with large circular double stranded DNA genomes, are unique because of their production of two different phenotypes of viruses during their infection cycle, and their extreme host specificity. Baculoviruses replicate only in invertebrates, and many isolates exhibit a very specific host range, infecting only one or a few insect genera. It is this strict species specificity which makes the study of baculoviruses so interesting. 

The objectives of baculovirus research have focused on: 

  • their use as biological pest control agents, 
  • their use as very efficient eukaryotic expression vectors (BEVs). 
  • important model viruses for studying the processes of gene regulation and particularly DNA replication in invertebrates. 
  • the potential use of baculoviruses as vectors in gene therapy. 
Thus, although they do not replicate in mammalian cells, baculoviruses can attach to and localize their genomes to the nucleus of these cells.
  • Why do they not then replicate? 
  • Why do they only replicate in insects, with a very strict host specificity? 
  • What factors regulate this strict host range?

The fundamental research in my laboratory is directed towards examining some of these concepts. Since genome replication is an early event in the virus replication cycle, understanding the temporal regulation of gene expression leading to the initiation of DNA replication and late gene expression will provide clues about host range specificity (for a review, see: Carstens, 2009).

We have been using Baculovirus, particularly an isolate of the Alphabaculovirus type species virus Autographa californica nucleopolyhedrovirus as a model (for a review, see: Carstens, 2012). The process of insect killing by baculoviruses is largely due to viraemia and generalized infection of tissues throughout the insect, a process that takes many days to kill the host insect, during which time, crop or forest damage due to insect feeding continues. By understanding the mechanisms of viral replication and interaction with host cell regulation, the genes involved in viral pathogenesis will be identified and exploited in new generation viruses for insect pest control. In addition, genes critical to establishing virus host range and virulence are being studied in order to learn which genes can be manipulated safely in designing new biological pesticides. At the same time, our research is leading to a greater understanding of the mechanism of baculovirus DNA replication and the functional significance of viral genes during this process. These studies will enable us to understand the restriction of baculovirus replication in nonpermissive systems, including mammalian cells.

Our research has been funded by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada


NSERC

Last modified: 2016 10 31