Fibroblast growth factor (FGF) was originally identified in the mid of 1970s in the pituitary of brain extracts and possesses mitogenic activity for murine fibroblasts. The genes of FGF family have been identified in all metazoan from nematode to mice and humans but not in bacteria or yeast, highlighting its importance in a variety of multicellular biological processes such as mitogenesis, angiogenesis, cell proliferation, differentiation and cell migration (12). The role of FGF in many of these processes is conserved in a variety of organisms, while inappro-priate expression of some fgfs may lead to cancer (13, 24). FGFs can bind heparin or heparin sulfate proteoglycans to form oligomers. This complex interacts specifically with FGF receptors (FGFRs), a group of transmembrane tyrosine kinases that are activated upon FGF binding leading to receptor dimerization and autophosphorylation. The activated FGFRs then stimulate the signal transduction pathways (24). It is notable that an fgf homologue (vfgfs) has been identified in baculoviruses, but not in other viruses and microorganisms so far (23).
The vfgf is present in all baculoviruses that infect lepidoptera, whose genomes have been sequenced so far (1, 20), suggesting that vfgf plays an essential role in the infection cycle of lepidopteran baculoviruses. It has been demonstrated that both Autographa califor-nica nucleopolyhedrovirus (AcMNPV) and Bombyx mori NPV (BmNPV) encode functional vFGF, which share some conservative properties common to better characterized vertebrate and nematode FGF, such as structural features, heparin affinity and chemotatic function (6). Moreover, BmNPV vfgf is involved in efficient virus production in BmN cells and B. mori larvae (17); however, the AcMNPV lacking vfgf recombinant virus has no obvious effect on virus production and protein or DNA synthesis relative to wild type virus both in vitro and in vivo (7). These results imply that the vfgf has functionally differen-tiated during viral evolution even in those baculovi-ruses with close relative, such as AcMNPV and BmNPV belonged to group Ⅰ NPV. So, it will be very interesting to analyze the vfgfs from baculovirus with evolutional distance, such as Helicoverpa armigera NPV (HearNPV) of group Ⅱ NPVs.
HearNPV contains a DNA genome of 135 kb encoding 135 open reading frames (ORFs) of 50 amino acids (aa) or more and ORF113 encodes a putative vfgf homolog (3). In this study, we carried out a detailed transcriptional analysis, evaluated some biochemical characteristics of vFGF compatible with the function of other known FGFs, and assess its properties in the specific chemoattraction of cells.
The ORF 113 of Heliocoverpa armigera Single Nucleopolyhedrovirus Encodes a Functional Fibroblast Growth Factor*
- Received Date: 30 April 2008
- Accepted Date: 12 May 2008
Abstract: Abstract: Fibroblast growth factor (FGF) is a key regulator of developmental processes. A FGF homolog (vFGF) is found in all lepidopteran baculoviruses. Autographa californica nucleopolyhedrovirus (AcMNPV) and Bombyx mori NPV (BmNPV) vFGFs are chemotactic factors. Here we analyzed the vfgf of Helicoverpa armigera NPV (HearNPV), a group II NPV. The HearNPV vfgf transcripts were detected from 18 to 96 h post-infection (hpi) of Hz-AM1 cells with HearNPV and encoded a 36 kDa protein, which was secreted into the culture medium. HearNPV vFGF had strong affinity to heparin, a property important for FGF signaling via an FGF receptor. Unlike its AcMNPV homolog, HearNPV vFGF specially chemoattracted Hz-AM1, but not other insect cells such as Sf9 and Se-UCR and not the mammalian cells 293 and HepG2. HearNPV vFGF is also associated with the envelope of BV but is absent in occlusion-derived virus, which coordinated to the chemotatic activity analysis.