The
serpin family of
serine proteinase inhibitors plays key roles in a variety of biochemical pathways. In insects, one of the important functions carried out by
serpins is regulation of the
phenoloxidase (PO) cascade - a pathway that produces
melanin and other compounds that are important in insect humoral immunity. Recent sequencing of the baculovirus Hemileuca sp. nucleopolyhedrovirus (HespNPV) genome revealed the presence of a gene, hesp018, with homology to insect
serpins. To our knowledge, hesp018 is the first viral
serpin homologue to be characterized outside of the chordopoxviruses. The Hesp018
protein was found to be a functional
serpin with inhibitory activity against a subset of
serine proteinases. Hesp018 also inhibited PO activation when mixed with lepidopteran haemolymph. The Hesp018
protein was secreted when expressed in lepidopteran cells and a baculovirus expressing Hesp018 exhibited accelerated production of viral progeny during in vitro
infection. Expression of Hesp018 also reduced
caspase activity induced by baculovirus
infection, but caused increased
cathepsin activity. In infected insect larvae, expression of Hesp018 resulted in faster larval melanization, consistent with increased activity of viral
cathepsin. Finally, expression of Hesp018 increased the virulence of a prototype baculovirus by fourfold in orally infected neonate Trichoplusia ni larvae. Based on our observations, we hypothesize that hesp018 may have been retained in HespNPV due to its ability to inhibit the activity of select host
proteinases, possibly including
proteinases involved in the PO response, during
infection of host insects.