Research

Viral Gene Regulation

Autographa californica nucleopolyhedrosis virus (AcMNPV) encodes about 150 genes in roughly three times (early, late, and very late phases) after infection of a permissive cell.  In general, genes expressed at an earlier phase may serve as regulatory factors for the subsequent phase.  Thus, the virus can strategically coordinate the expression of over 100 genes in harmony, where each gene product is functional in a timely fashion.  In order for the virus to achieve this feat, some genes need to be activated, others repressed, gene products need to be produced at the right levels and have the ability to interact with other viral or host factors or/and nucleic acids. 

We are studying how genes are regulated and how this gives the virus an advantage over host cells.  We are looking at the interactions of transcription factors, host determination factors, and other genes with the host and viral machineries.  What are these specific insect factors that render the host permissive to infection?  It is important to delineate the involvement of the host machinery during the infection cycle of the virus in order to understand which host proteins serve as targets facilitating successful virus replication.   There are probably complex interactions involving a number of cellular factors, but the identification of specific key players will lead to inroads to explore specific viral or cellular pathways. 

Baculoviruses are like many DNA viruses in that they transcribe their early genes using the host DNA-directed RNA polymerase, RNA polymerase II.  However, they are unlike most viruses in their strategy to transcribe their late and very late genes. Baculoviruses use a novel virally encoded DNA-directed RNA polymerase to transcribe genes at late stages in their replication cycle.  In fact, baculoviruses are the only known nuclear replicating DNA viruses that encode a DNA-directed RNA polymerase.  This may be a strategy used to outcompete host transcription or stimulate late viral gene transcription. The promoters of the genes composing the baculovirus polymerase are non-conventional early viral promoters and may be regulated differently than other well-characterized early promoters. The requirements to stimulate these promoters will be determined by transient reporter gene expression assays. These studies will aid in improving gene expression vectors that in almost every case use this polymerase to transcribe foreign genes.