Autophagy promotes replication of Bombyx mori Nucleopolyhedrovirus in insect cells.

BmNPV is a pathogen that infects silkworms exclusively. Although the interaction between BmNPV and the silkworm has been widely noticed and studied, its specific mechanism has still not been elucidated. In this study, we investigated whether BmNPV infection induces the onset of host cell autophagy to enhance viral replication. We observed a significant increase in double- or single-membrane vesicles and an accumulation of enhanced green fluorescent protein eGFP-ATG8 spots in virus-infected cells 72 h after BmNPV infection, accompanied by a conversion of ATG8 to ATG8-PE. In addition, we observed changes in the mitochondrial morphology of BmN cells after BmNPV infection by transmission electron microscopy. By detecting the mitochondrial membrane potential, we found that BmNPV infection resulted in the decrease of mitochondrial membrane potential, and that eGFP-ATG8 was able to co-localise with mitochondria after virus infection of the cells. Moreover, the use of drugs to regulate the occurrence of autophagy affects the replication of cellular BmNPV. Our data demonstrates that BmNPV infection induces host cell autophagy and leads to cellular mitochondrial damage, which in turn may lead to mitochondrial autophagy, and that BmNPV-induced host autophagy promotes its replication in cells. These findings will provide clues for further understanding of host-virus interactions.

Epidemiological characteristics of first-time SARS-CoV-2 Omicron infection among hospital staff in Chengdu, China.

BACKGROUND: After China ended its 'dynamic zero-COVID policy' on 7 December 2022, a large-scale outbreak of SARS-CoV-2 Omicron infections emerged across the country. We conducted a hospital-wide prospective study to document the epidemiological characteristics of the outbreak among healthcare workers in a hospital of Chengdu, where no previous staff SARS-CoV-2 infections were detected. METHODS: All hospital staff members were invited to complete an online questionnaire on COVID-19 in January 2023, and SARS-CoV-2 infection cases were followed up by telephone in June 2023 to collect data on long COVID. Univariable and multivariable logistic regression analyses were performed to evaluate factors associated with SARS-CoV-2 infection. RESULTS: A total of 2,899 hospital staff (93.5%) completed the online questionnaire, and 86.4% were infected with SARS-CoV-2 Omicron. The clinical manifestations of these patients were characterized by a high incidence of systemic symptoms. Cough (83.4%), fatigue (79.8%) and fever (74.3%) were the most frequently reported symptoms. Multivariable logistic analysis revealed that females [adjusted odds ratio (aOR): 1.42, 95% confidence interval (CI): 1.07-1.88] and clinical practitioners (aOR: 10.32, 95% CI: 6.57-16.20) were associated with an increased risk of SARS-CoV-2 infection, whereas advanced age ≥ 60 years (aOR: 0.30, 95% CI: 0.19-0.49) and a three-dose COVID-19 vaccination with the most recent dose administered within 3 months before 7 December 2022 (aOR: 0.44, 95% CI: 0.23-0.87 for within 1 month; aOR: 0.46, 95% CI: 0.22-0.97 for within 1-3 months) were associated with reduced risk. Among the cases, 4.27% experienced long COVID of fatigue, brain fog or both, with the majority reporting minor symptoms. CONCLUSION: Our findings provide a snapshot of the epidemiological situation of SARS-CoV-2 infection among healthcare workers in Chengdu after China's deregulation of COVID-19 control. Data in the study can aid in the development and implementation of effective measures to protect healthcare workers and maintain the integrity of healthcare systems during challenging times such as a rapid and widespread Omicron outbreak.

Silk films with distinct surface topography modulate plasma membrane curvature to polarize macrophages.

The physical properties of a biomaterial play a vital role in modulating macrophage polarization. However, discerning the specific effects of individual parameters can be intricate due to their interdependencies, limiting the mechanism underlying a specific parameter on the polarization of macrophages. Here, we engineered silk fibroin (SF) films with tunable surface roughness while maintaining similar physical properties by combining casting and salting out techniques. We demonstrate that increased surface roughness in SF films promotes M2-like macrophage polarization, characterized by enhanced secretion of anti-inflammatory cytokines. Transcriptomic analysis unveils the modulation of genes associated with extracellular matrix-cell interactions, highlighting the role of surface topography in regulating cellular processes. Mechanistically, we show that surface roughness induces macrophage membrane curvature, facilitating integrin αv endocytosis and thereby inhibiting the integrin-NF-kB signaling pathway. In vivo implantation assays corroborate that rough SF films substantially mitigate early inflammatory responses. This work establishes a direct link between surface roughness and intracellular signaling in macrophages, adding to our understanding of the biomaterial surface effect at the material-cell interface and bringing insights into material design.

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.