Silk sericin as building blocks of bioactive materials for advanced therapeutics.

Silk sericin is a class of protein biopolymers produced by silkworms. Increasing attention has been paid to silk sericin for biomedical applications in the last decade, not only because of its excellent biocompatibility and biodegradability but also due to the pharmacological activities stemming from its unique amino acid compositions. In this review, the biological properties of silk sericin, including curing specific diseases and promoting tissue regeneration, as well as underlying mechanisms are summarized. We consider the antioxidant activity of silk sericin as a fundamental property, which could account for partial biological activities, despite the exact mechanisms of silk sericin's effect remaining unknown. Based on the reactive groups on silk sericin, approaches of bottom-up fabrication of silk sericin-based biomaterials are highlighted, including non-covalent interactions and chemical reactions (reduction, crosslinking, bioconjugation, and polymerization). We then briefly present the cutting-edge advances of silk sericin-based biomaterials applied in tissue engineering and drug delivery. The challenges of silk sericin-based biomaterials are proposed. With more bioactivities and underlying mechanisms of silk sericin uncovered, it is going to boost the therapeutic potential of silk sericin-based biomaterials.

BmCH25H, a vertebrate interferon-stimulated gene(ISG) homolog, inhibits BmNPV infection dependent on its hydroxylase activity in Bombyx mori.

Cholesterol-25-hydroxylase (CH25H) has been identified as an interferon-stimulated gene (ISG) in mammals that exerts its antiviral effects by catalyzing the conversion of cholesterol to 25-hydroxycholesterol (25HC). However, invertebrates lack an antiviral system homologous to vertebrate interferons (IFNs) because the genomes of invertebrates do not encode IFN-like cytokines. Nevertheless, CH25H is present in insect genomes and it therefore deserves further study of whether and by which mechanism it could exert an antiviral effect in invertebrates. In this study, the Bombyx mori CH25H (BmCH25H) gene, of which the encoded protein has high homology with other lepidopteran species, was identified and located on chromosome 9. Interestingly, we found that the expression of BmCH25H was significantly upregulated in B. mori nucleopolyhedrovirus (BmNPV) -infected BmN cells and silkworm (B. mori) larvae at the early infection stage. The inhibitory effect of BmCH25H on BmNPV replication was further demonstrated to depend on its catalytic residues to convert cholesterol to 25HC. More importantly, we demonstrated that during BmNPV infection, BmCH25H expression was increased through the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, similar to the induction of ISGs following virus infection in vertebrates. This is the first report that CH25H has antiviral effects in insects; the study also elucidates the regulation of its expression and its mechanism of action.

Apolipoprotein D facilitate the proliferation of BmNPV.

The silkworm, Bombyx mori, a model Lepidopteran specie, is an important economic insect. It is specifically infected by Bombyx mori nucleopolyhedrovirus (BmNPV), causing huge losses to the sericulture industry. Therefore, the understandings of the interaction mechanism between BmNPV and the host will help to provide the theoretical basis for the sericulture industry to control BmNPV. Apolipoprotein D (ApoD) is a member of lipid transport family and capable of binding to a variety of lipophilic ligands. ApoD is mainly used in neurodegenerative disease research in mammals, and there is little research on ApoD against viruses. Here, we explored the effects of Bombyx mori Apolipoprotein D (BmApoD) on BmNPV replication. We knocked out and overexpressed BmApoD in BmN cells and infected them with Bombyx mori nucleopolyhedrovirus (BmNPV). The results showed that BmApoD promote the replication of BmNPV in BmN cells. It was also confirmed that BmApoD promote the replication of BmNPV after knocking down BmApoD in silkworm larvae. This study is the first to explore the role of ApoD in insect-virus interactions, providing new insights into the functional role of ApoD.

Sirt5 Inhibits BmNPV Replication by Promoting a Relish-Mediated Antiviral Pathway in Bombyx mori.

Silent information regulators (Sirtuins) belong to the family of nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases (HDACs) that have diverse functions in cells. Mammalian Sirtuins have seven isoforms (Sirt1-7) which have been found to play a role in viral replication. However, Sirtuin members of insects are very different from mammals, and the function of insect Sirtuins in regulating virus replication is unclear. The silkworm, Bombyx mori, as a model species of Lepidoptera, is also an important economical insect. B. mori nucleopolyhedrovirus (BmNPV) is a major pathogen that specifically infects silkworms and causes serious losses in the sericulture industry. Here, we used the infection of the silkworm by BmNPV as a model to explore the effect of Sirtuins on virus replication. We initially knocked down all silkworm Sirtuins, and then infected with BmNPV to analyze its replication. Sirt2 and Sirt5 were found to have potential antiviral functions in the silkworm. We further confirmed the antiviral function of silkworm Sirt5 through its effects on viral titers during both knockdown and overexpression experiments. Additionally, Suramin, a Sirt5 inhibitor, was found to promote BmNPV replication. In terms of molecular mechanism, it was found that silkworm Sirt5 might promote the immune pathway mediated by Relish, thereby enhancing the host antiviral response. This study is the first to explore the role of Sirtuins in insect-virus interactions, providing new insights into the functional role of members of the insect Sirtuin family.