Editorial [Hot Topic:Current Perspectives on Baculovirus (Guest Editor: M.J. Fraser, Jr.)]

The field of baculovirus research has provided many important and novel insights into virus-host interactions and pathology, DNA virus transcriptional regulation and replication mechanisms, virus/host co-evolution and genome interactions, and basic eukaryotic cellular functions such as apoptosis and nuclear importation. Many of these insights have already proven beneficial in developing the baculovirus expression vector system and derivative protein expression systems for insect cells, and for guiding similar observations in human disease systems. The impact of the insect cell-based protein expression systems for eukaryotic gene expression and rapid characterization of gene products is enormous, and continues to provide a rich avenue of practical research and biotechnology development. All in all, the relatively small research community that has studied baculovirus systems over the years has contributed abundantly to both fundamental and practical science. The baculovirus replication cycle is a relatively complex program of regulated transcription that involves the coordinate activation and/or repression of over 40 genes, some of which are highly productive for their gene products. The highly productive p10 and polyhedrin genes have been harnessed for protein expression in infected cells. However, the complex regulation that leads to their abundant expression has yet to be duplicated outside the context of the infected cells. Such a virus-free system could present a significant advancement for protein expression in insect cells, and can only be achieved with more and better understanding of the baculovirus regulatory cascade. This issue of Current Drug targets focuses attention on current Baculovirus research in an effort to not only review what has been discovered, but to also provide a foundation for further useful discoveries in this biotechnologically relevant system. The article by Herniou and Jehle on baculovirus phylogeny and evolution covers our current state of knowledge about the relatedness of baculoviruses and their co-evolution with their hosts from a sequence analysis perspective, while van Oers and Vlak review the functional relatedness and organization of genes among the baculoviruses. Three articles exemplify the importance of baculovirus research in defining important aspects of cellular function during DNA virus replication. Clem discusses the relationship between baculovirus pathology and apoptosis, which follows upon observations that were among the first to be made for suppression of apoptosis in a virus/host system. Volkman details the role of nuclear actin in baculovirus pathology and assembly, an observation that may have relevance for other nuclear replicating viruses. Braunagel and Summers elucidate the molecular biology of occlusion-derived virus envelope assembly, and in the process define an integral membrane protein trafficking pathway involving a unique importin first identified in this system. Two articles review transcriptional regulation and replication of these viruses. Vanarsdall, Mikhailov, and Rohrmann present our current understanding of DNA replication among the baculoviruses, defining the function of several important gene products in this process. Passarelli and Guarino review the extensive database of information characterizing the activity and function of late and very late genes important for the regulation of baculovirus host range, activation of polyhedron and p10 promoters, and replication of the genome. Finally, two articles focus on baculoviruses as protein expression systems. Shi and Jarvis discuss the characteristics of the N-glycosylation pathway in the baculovirus-insect cell system and some practical solutions to correcting differences between this pathway and that of mammalian cells. Condreay and Kost review the current state of baculovirus expression vector technology as well as the accumulating evidence for baculoviruses as safe and effective gene transduction vectors for animal cells. It is my hope that this issue of Current Drug Targets will enlighten the readers with the many exciting observations that have flowed from this unique and valuable biological system, and will help stimulate continued research interest in this productive experimental model.