Table 2. Selected highly differentially expressed genes following pathogenic infection of midgut tissue.
| Category/ Name | Known/ Possible function |
|---|---|
| Physical barrier | |
| CPH43 | putative cuticle gene; involved in larval molting [31] |
| Immune responses | |
| IBP2 | highly homologous to IGFBP7 in vertebrates (tumor-suppressive function leading to apoptosis); involved in immune and endocrine responses [32–37] |
| insulin signaling pathway is reported to be involved in the defense against pathogens in C. elegans [38] | |
| vertebrate insulin activates the extracellular signal-regulated kinase (ERK) in the mosquito gut; has an antiviral role in Drosophila cells and insect gut epithelium [39] | |
| PGRP LB-like | behaves as an amidase; hydrolyzes Gram- bacteria peptidoglycan and is activated by them; indirectly acts as negative regulator of the IMD pathway, thus balancing homeostasis and immune response activation [40, 41] |
| Proteolytic enzymes | |
| Caspase-8-like | death receptor-associated initiator caspase-8 is expected to be activated upon reovirus infection in the case of reovirus-induced apoptosis [42–45] |
| CPB | up-regulated in the midgut of Anopheles gambiae mosquitoes infected with Plasmodium falciparum parasite, significantly reduced growth and development of rodent parasite P. berghei in mosquitos fed on infected mice immunized against CPB [46] |
| Trypsin-like protease precursor | alkaline protease; active in the silkworm midgut alkaline environment; participates in the hydrolysis of incoming food and probably also of viral polyhedra, thus mediating release of occluded viruses and infection of midgut columnar epithelial cells [47] |
| trypsin-like protease is down-regulated in BmDNV-Z and BmNPV-infected silkworm strains susceptible to the respective viruses, up-regulated in BmNPV-infected silkworm strain [47, 48] | |
| facilitates DENV-2 virus infection in Aedes aegypti [49] | |
| Zinc carboxypeptidase A1-like (CPA1) | Metallocarboxypeptidase ACI, a zinc carboxypeptidase A1 (CPA1) inhibitor, is expressed by Ascaris (human intestinal parasite) to enhance its survival during infection [50] |
| Heat-shock proteins | |
| HSPs; HSCs | molecular chaperones in various cellular processes; danger signals thus activating host immune response [51, 52] |
| HSPs and HSCs are necessary for efficient BmNPV proliferation in Bombyx cells as well as for PCV2 virus expansion in porcine cells [53–55] | |
| sHSPs are induced in BmCPV-infected larval midguts [18] | |
| Hsp25 has antiviral role in reovirus-infected murine cells [56]; HSC70 is up-regulated in BmCPV-infected silkworms (72hpi) [18]; Hsc70t and HSP105 are induced by reovirus infection in murine cells [57] | |
| Metabolic enzymes | |
| DCXR | converts L-xylulose in xylitol (carbohydrate metabolism); reduces the highly reactive α-dicarbonyl compounds (DCs) with endogenous/ xenobiotic origin (detoxifying enzyme) [58] |
| DHS-21 (DCXR ortholog) is essential for normal life-span and reproduction of C. elegans [59] | |
| Esterase FE4-like | esterases hydrolyze and inactivate insecticides (insecticide resistance), but also metabolize pathogen-secreted toxic compounds (host response) [60]; as counter-mechanism, pathogens may synthesize inhibitors against such esterase function to cause down-regulation of esterase genes |
| Hormonal signaling | |
| NPLP4E | neuropeptides: signaling molecules playing key roles in insects due to their involvement in developmental, reproductive, metabolic and behavioral processes; expressed in several tissues (brain, epidermis, ovary, prothoracic gland); possibly involved in molting regulation [61] |
| NPLP4E maybe carries out additional functions in the midgut (here was first detected to be expressed) [31, 62] | |
| Uncharacterized | |
| LOC101735726 | possible role in the physiological process of DNA replication and maintenance (S5 Fig.) which may be hindered due to BmCPV presence in the midgut |
The list represents genes with high differential expression levels during pathogenic infection detected by deep sequencing analysis that were also validated by qRT-PCR. The selected genes are categorized according to their function. Relevant studies representing similar responses to infection are also listed.