In thepast 2decades,synthetic biologists have applied systematic engineering principles to genetic circuit design to devise biological systems with bespoke behaviors,such as Boolean logic gates,signal filters,oscillat...In thepast 2decades,synthetic biologists have applied systematic engineering principles to genetic circuit design to devise biological systems with bespoke behaviors,such as Boolean logic gates,signal filters,oscillators,state machines,perceptrons,and genetic controllers[1,2].Following a bottom-up strategy,the genetic circuits are designed by assembling a set of well-characterized biological components,or genetic parts[3],and optimized through the iterative Design-Build-Test-Learn(DBTL)cycles.展开更多
Patients with an influenza virus infection can be complicated by acute encephalopathy and encephalitis. To investigate the immune reactions involved in the neurocomplication, mouse microglia and astrocytes were isolat...Patients with an influenza virus infection can be complicated by acute encephalopathy and encephalitis. To investigate the immune reactions involved in the neurocomplication, mouse microglia and astrocytes were isolated, infected with human H1N1 and avian H5N1 influenza viruses, and examined for their immune responses. We observed homogeneously distributed viral receptors, sialic acid （SA）-a2,3-Galactose （Gal） and SA-a2,6-Gal, on microglia and astrocytes. Both viruses were replicative and productive in microglia and astrocytes. Virus-induced apoptosis and cytopathy in infected cells were observed at 24 h post-infection （p.i.）. Expression of IL-1β, IL-6 and TNF-a mRNA examined at 6 h and 24 h p.i. was up-regulated, and their expression levels were considerably higher in H5N1 infection. The amounts of secreted proinflammatory IL-1β, IL-6 and TNF-a at 6 h and 24 h p.i. were also induced, with greater induction by H5N1 infection. This study is the first demonstration that both human H1N1 and avian H5N1 influenza viruses can infect mouse microglia and astrocytes and induce apoptosis, cytopathy, and proinflammatory cytokine production in them in vitro. Our results suggest that the direct cellular damage and the consequences of immunopathological injury in the CNS contribute to the influenza viral pathogenesis. Cellular ＆ Molecular Immunology.展开更多
基金Fundamental Research Funds for the Central Universities,Grant/Award Number:226-2022-00214National Key R&D Program of China,Grant/Award Number:2023YFF1204500+1 种基金“Pioneer”and“Leading Goose”R&D Program of Zhejiang,Grant/Award Number:2024C03011National Natural Science Foundation of China,Grant/AwardNumbers:32271475,32320103001。
文摘In thepast 2decades,synthetic biologists have applied systematic engineering principles to genetic circuit design to devise biological systems with bespoke behaviors,such as Boolean logic gates,signal filters,oscillators,state machines,perceptrons,and genetic controllers[1,2].Following a bottom-up strategy,the genetic circuits are designed by assembling a set of well-characterized biological components,or genetic parts[3],and optimized through the iterative Design-Build-Test-Learn(DBTL)cycles.
基金supported by grants from National Natural Science Foundation of China(No.30571674 and No.30771988)Guangdong Natural Science Foundation(No.05008347 and No.04020239).
文摘Patients with an influenza virus infection can be complicated by acute encephalopathy and encephalitis. To investigate the immune reactions involved in the neurocomplication, mouse microglia and astrocytes were isolated, infected with human H1N1 and avian H5N1 influenza viruses, and examined for their immune responses. We observed homogeneously distributed viral receptors, sialic acid （SA）-a2,3-Galactose （Gal） and SA-a2,6-Gal, on microglia and astrocytes. Both viruses were replicative and productive in microglia and astrocytes. Virus-induced apoptosis and cytopathy in infected cells were observed at 24 h post-infection （p.i.）. Expression of IL-1β, IL-6 and TNF-a mRNA examined at 6 h and 24 h p.i. was up-regulated, and their expression levels were considerably higher in H5N1 infection. The amounts of secreted proinflammatory IL-1β, IL-6 and TNF-a at 6 h and 24 h p.i. were also induced, with greater induction by H5N1 infection. This study is the first demonstration that both human H1N1 and avian H5N1 influenza viruses can infect mouse microglia and astrocytes and induce apoptosis, cytopathy, and proinflammatory cytokine production in them in vitro. Our results suggest that the direct cellular damage and the consequences of immunopathological injury in the CNS contribute to the influenza viral pathogenesis. Cellular ＆ Molecular Immunology.
