An intestinal mucin is the target substrate for a baculovirus enhancin

Abstract

An invertebrate intestinal mucin (IIM) was identified from a lepidopterous insect, Trichoplusia ni. The IIM is a major protein constituent of the peritrophic membrane that facilitates the digestive process, as well as protecting invertebrate digestive tracts from microbial infections. The IIM demonstrated biochemical characteristics similar to vertebrate mucins, but exhibited strong association with the chitin-containing peritrophic membrane matrix. We have demonstrated that a baculovirus enhancin, which is encoded and carried by specific baculoviruses, has mucin-degrading activity both in vitro and in vivo. The in vivo degradation of IIM by enhancin was correlated with the enhancement of baculovirus infections in insects. These findings have shown that viruses have evolved a novel strategy to overcome intestinal mucinous barriers against microorganisms by utilizing a mucin-degrading enzyme.

Genome sequence of Yersinia pestis, the causative agent of plague

“…Strikingly, a protein showing weak, but signi®cant, similarity only to the enhancins encoded uniquely by baculoviral pathogens of insects was identi®ed (YPO0339, 25% identity) in a region of low G + C content,¯anked by a transfer RNA gene and transposase fragments, suggesting horizontal acquisition. During baculoviral pathogenesis, the proteolytic activity of enhancin damages the peritrophic membrane, which normally provides a physical barrier against microbial pathogens in the insect midgut 13 and the product of YPO0339 may be important in colonization of the¯ea by Y. pestis. Interestingly, PCR shows (R.W.T., data not shown) that the tca insecticidal toxin genes are also present in Y. pseudotuberculosis IP 32953 (virulent serotype I strain).…”

Role of enhancin in Mamestra configurata nucleopolyhedrovirus virulence: selective degradation of host peritrophic matrix proteins

“…Western blot analysis of the PM proteins associated with faecal pellets from fifth-instar larvae, using an anti-TnIIM antibody, was done as described previously (Wang & Granados, 1997a). The PM associated with faecal pellet samples showed predominantly high-molecular-mass bands at .200 kDa, approximately 200 kDa and between 116 and 97 kDa (Fig.…”

“…In order for baculovirus ODVs to infect insect midgut cells, they must first cross the peritrophic matrix (PM), a semipermeable sheath that is composed of chitin microfibrils and proteins, lining the midgut of most insect species (Wang & Granados, 1997a). The PM protects the midgut epithelium from mechanical damage, toxic compounds and pathogens, regulates nutrient uptake by compartmentalizing digestive processes and prevents excretion of digestive enzymes by providing a means for enzyme recycling (reviewed by Hegedus et al, 2009).…”

“…The protective feature of the PM is in part due to insect intestinal mucins (IIMs) that are common and predominant features of the insect PMs (Toprak et al, 2010a). These proteins contain O-glycosylated regions referred to as mucin domains (MDs) that are important in protecting (Wang & Granados, 1997a; Devenport et al, 2006).Early studies showed that co-feeding of GV OBs with NPV OBs significantly increased the infectivity and virulence of the NPV for its natural host even in the absence of any actual GV infection (Tanada, 1959;Yamamoto & Tanada, 1978;Zhu et al, 1989). In the case of Trichoplusia ni granulovirus (TnGV), this enhancement of NPV infectivity was linked to degradation of the host insect PM and increased PM permeability caused by a metalloprotease, enhancin, that was associated with the OBs (Lepore et al, 1996;Peng et al, 1999).…”

“…Late in the infection cycle, nucleocapsids are enveloped (single or multiple nucleocapsids per virion) by membranes formed within the infected host-cell nucleus and these virions are subsequently occluded within proteinaceous crystals or occlusion bodies (OBs). These ODVs are infectious to insect midgut cells upon ingestion by a susceptible host.In order for baculovirus ODVs to infect insect midgut cells, they must first cross the peritrophic matrix (PM), a semipermeable sheath that is composed of chitin microfibrils and proteins, lining the midgut of most insect species (Wang & Granados, 1997a). The PM protects the midgut epithelium from mechanical damage, toxic compounds and pathogens, regulates nutrient uptake by compartmentalizing digestive processes and prevents excretion of digestive enzymes by providing a means for enzyme recycling (reviewed by Hegedus et al, 2009).…”