RÉSUMÉ
Southern Africa Territories 2 (SAT2) foot-and-mouth disease (FMD) has crossed long-standing regional boundaries in recent years and entered the Middle East. However, the existing vaccines offer poor cross-protection against the circulating strains in the field. Therefore, there is an urgent need for an alternative design approach for vaccines in anticipation of a pandemic of SAT2 Foot-and-mouth disease virus (FMDV). The porcine parvovirus (PPV) VP2 protein can embed exogenous epitopes into the four loops on its surface, assemble into virus-like particles (VLPs), and induce antibodies and cytokines to PPV and the exogenous epitope. In this study, chimeric porcine parvovirus VP2 VLPs (chimeric PPV-SAT2-VLPs) expressing the T-and/or B-cell epitopes of the structural protein VP1 of FMDV SAT2 were produced using the recombinant pFastBac™ Dual vector of baculoviruses in Sf9 and HF cells We used the Bac-to-Bac system to construct the recombinant baculoviruses. The VP2-VLP--SAT2 chimeras displayed chimeric T-cell epitope (amino acids 21-40 of VP1) and/or the B-cell epitope (amino acids 135-174) of SAT FMDV VP1 by substitution of the corresponding regions at the N terminus (amino acids 2-23) and/or loop 2 and/or loop 4 of the PPV VP2 protein, respectively. In mice, the chimeric PPV-SAT2-VLPs induced specific antibodies against PPV and the VP1 protein of SAT2 FMDV. The VP2-VLP-SAT2 chimeras induced specific antibodies to PPV and the VP1 protein specific epitopes of FMDV SAT2. In this study, as a proof-of-concept, successfully generated chimeric PPV-VP2 VLPs expressing epitopes of the structural protein VP1 of FMDV SAT2 that has a potential to prevent FMDV SAT2 and PPV infection in pigs.
Sujet(s)
Anticorps antiviraux , Antigènes viraux , Protéines de capside , Virus de la fièvre aphteuse , Fièvre aphteuse , Parvovirus porcin , Vaccins à pseudo-particules virales , Vaccins antiviraux , Animaux , Virus de la fièvre aphteuse/immunologie , Virus de la fièvre aphteuse/génétique , Souris , Fièvre aphteuse/immunologie , Fièvre aphteuse/prévention et contrôle , Fièvre aphteuse/virologie , Protéines de capside/immunologie , Protéines de capside/génétique , Parvovirus porcin/immunologie , Parvovirus porcin/génétique , Anticorps antiviraux/immunologie , Anticorps antiviraux/sang , Vaccins antiviraux/immunologie , Vaccins antiviraux/génétique , Vaccins à pseudo-particules virales/immunologie , Vaccins à pseudo-particules virales/génétique , Suidae , Immunité humorale , Immunité cellulaire , Déterminants antigéniques des lymphocytes T/immunologie , Déterminants antigéniques des lymphocytes T/génétique , Déterminants antigéniques des lymphocytes B/immunologie , Déterminants antigéniques des lymphocytes B/génétique , Sérogroupe , Souris de lignée BALB C , Femelle , Épitopes/immunologie , Épitopes/génétique , Cellules Sf9 , Anticorps neutralisants/immunologie , Anticorps neutralisants/sangRÉSUMÉ
African swine fever (ASF) is a highly contagious and hemorrhagic disease caused by infection with the African swine fever virus (ASFV), resulting in a mortality rate of up to 100%. Currently, there are no effective treatments and commercially available vaccines for ASF. Therefore, it is crucial to identify biochemicals derived from host cells that can impede ASFV replication, with the aim of preventing and controlling ASF. The ASFV is an acellular organism that promotes self-replication by hijacking the metabolic machinery and biochemical resources of host cells. ASFV specifically alters the utilization of glucose and glutamine, which are the primary metabolic sources in mammalian cells. This study aimed to investigate the impact of glucose and glutamine metabolic dynamics on the rate of ASFV replication. Our findings demonstrate that ASFV infection favors using glutamine as a metabolic fuel to facilitate self-replication. ASFV replication can be substantially inhibited by blocking glutamine metabolism. The metabolomics analysis of the host cell after late-stage ASFV infection revealed a significant disruption of normal glutamine metabolic pathways due to the abundant expression of PLA (phenyllactic acid). Pretreatment with PLA also inhibited ASFV proliferation and glutamine consumption following infection. The metabolomic analysis also showed that PLA pretreatment greatly slowed down the metabolism of amino acids and nucleotides that depend on glutamine. The depletion of these building blocks directly hindered the replication of ASFV by decreasing the biosynthetic precursors produced during the replication of ASFV's progeny virus. These findings provide valuable insight into the possibility of pursuing the development of antiviral drugs against ASFV that selectively target metabolic pathways.
Sujet(s)
Virus de la peste porcine africaine , Peste porcine africaine , Lactates , Suidae , Animaux , Glutamine , Glucose , Polyesters/pharmacologie , Réplication virale , MammifèresRÉSUMÉ
BACKGROUND: Cyclin B2 (CCNB2), a member of the cyclin family, is an oncogene in multiple cancers, including nasopharyngeal carcinoma (NPC). However, the epigenetics mechanism for CCNB2 overexpression in NPC remains unclear. This study dissects the regulatory role of CCNB2 in NPC and the molecular mechanism. METHODS: Differentially methylated genes (DMG) and differentially expressed genes (DEG) were screened out in GSE52068 and GSE13597 databases, respectively, and candidate targets were identified by the Venn diagram. GO annotation and pathway enrichment analyses were performed on selected DMG and DEG, and a PPI network was constructed to pinpoint hub genes. PCR and qMSP were conducted to detect the expression and methylation of CCNB2 in cells. The siRNA targeting CCNB2 was transfected into NPC cells, and the migration, proliferation, cell cycle, epithelial-mesenchymal transition (EMT), tumorigenesis, and metastasis were examined. The upstream factor responsible for CCNB2 overexpression in NPC was explored. The p53 activity in NPC cells was assessed using western blot analysis. RESULTS: CCNB2 showed hypomethylation and overexpression in NPC. CCNB2 silencing inhibited cell migration, proliferation, cell cycle entry, and EMT. JMJD6 was overexpressed in NPC and upregulated CCNB2 through demethylation. JMJD6 reversed the effects of CCNB2 downregulation, resulting in elevated cellular activity in vitro and tumorigenic and metastatic activities in vivo. CCNB2 blocked the p53 pathway, while the p53 pathway inhibitor reversed the effect of CCNB2 silencing to increase the activity of NPC cells. CONCLUSIONS: JMJD6 enhanced CCNB2 transcription by demethylating CCNB2, thereby repressing the p53 pathway and promoting NPC progression.
Sujet(s)
Cycline B2 , Cancer du nasopharynx , Tumeurs du rhinopharynx , Protéine p53 suppresseur de tumeur , Humains , Lignée cellulaire tumorale , Mouvement cellulaire/génétique , Prolifération cellulaire/génétique , Cycline B2/génétique , Cycline B2/métabolisme , Transition épithélio-mésenchymateuse/génétique , Régulation de l'expression des gènes tumoraux , Jumonji Domain-Containing Histone Demethylases/métabolisme , Cancer du nasopharynx/génétique , Cancer du nasopharynx/anatomopathologie , Tumeurs du rhinopharynx/génétique , Tumeurs du rhinopharynx/anatomopathologie , Transduction du signal/génétique , Protéine p53 suppresseur de tumeur/génétique , Protéine p53 suppresseur de tumeur/métabolismeRÉSUMÉ
Modern nanotechnology has made zinc oxide nanomaterials (ZnO NMts) multifunctional, stable, and low cost, enabling them to be widely used in commercial and biomedical fields. With its wide application, the risk of human direct contact and their release into the environment also increases. This review aims to summarize the toxicity studies of ZnO NMts in vivo, including neurotoxicity, inhalation toxicity, and reproductive toxicity. The antibacterial and antiviral mechanisms of ZnO NMts in vitro and the toxicity to eukaryotic cells were summarized. The summary found that it was mainly related to reactive oxygen species (ROS) produced by oxidative stress. It also discusses the potential harm to body and the favorable prospects of the widespread use of antibacterial and antiviral in the future medical field. The review also emphasizes that the dosage and use method of ZnO NMts will be the focus of future biomedical research.