Since their first description in the late 1970s considerable efforts have been made to understand the origin, genomic organization, and impact of PDVs on the physiology of their lepidopteran hosts. In recent years, there has been explosive growth in data concerning the functional characterization of PDV virulence genes. Considering that reverse genetics approaches are impossible in these systems, authors have concentrated mainly on functional approaches using highly expressed genes and/or genes presenting conserved functional domains. So far functional characterizations have been performed mainly by in vitro biochemical assays and transient expression in non-host and sometimes host cell lines in vitro, and more rarely in vivo. Although it is debatable whether over-expression of genes in non-host cells is a relevant functional assay, these experiments enabled the identification of targeted pathways in the host. It is likely that in vivo certain gene viral products have a more subtle effect both in time and in space and that in the natural system a blend of genes and their products is necessary to ensure perfect host control. Surprisingly, in vivo use of RNAi has not yet been reported in larval parasitoid systems and has only been successfully performed with the egg parasitoid C. inanitus (Bonvin et al., 2005). Injection of double-stranded RNA of three CiBV genes into CiBV/venom containing eggs partially rescued lastinstar larvae from developmental arrest, indicating that these viral genes are involved in the inhibition of development (Bonvin et al., 2005). In the future, RNAi of viral genes or of their host targets, as has been done in a Manduca/parasitic nematode/ bacterial system (Eleftherianos et al., 2007) may provide new insights on PDV gene function and host deregulation.

Beyond their impact on host immunity and development PDV also target different aspects of lepidopteran host biology. For example, in a recent study it was also shown that the behaviour of caterpillars can be manipulated by a wasp (Glyptapanteles sp.): after the emergence of parasit-oid larvae from the host, the caterpillars protect the wasp cocoons against parasites and predators (Grosman et al, 2008). Since this wasp is associated with a bracovirus encoding PTPs it is conceivable that PDV might be involved in this striking effect of parasitism. Indeed a PTP was shown to be responsible for the manipulation of lepidopteran behaviour by baculoviruses, leading the infected caterpillar to climb to the top of the plant, thus favouring virus spread (Kamita et al., 2005). The fact that certain PDV effectors target signalling pathways potentially involved in a multitude of physiological systems could explain the pleiotropic effects of PDVs.

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