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A new microsporidian disease of the pond-reared ridgetail white prawn, Palaemon carinicauda, was found in China. Light microscopy, pathology, and scanning electron microscopy showed that the parasite infected the host's skeletal muscle tissue and formed spherical sporophorous vesicles (SPOVs). Electron microscopy revealed that its merogonic life stages developed in direct contact with the host cytoplasm. The sporogonic life stages underwent octosporoblastic sporogony with the formation of eight uninucleate spores in each SPOV. Fresh SPOVs were 5.4 ± 0.55 µm in diameter. The octospores were oval and measured 2.3 × 1.5 µm (fresh) and 1.96 × 1.17 µm (fixed). The isofilar polar filament was coiled with 9-10 turns and arranged in two rows. Phylogenetic analysis based on the SSU rRNA gene suggests that this microsporidium has close affinities with members of the genera Potaspora and Apotaspora, but represents an independent generic taxon. We therefore propose the establishment of a new genus and species (Paospora carinifang n. gen., n. sp.) within the family Spragueidae. We also propose a taxonomic revision to transfer Potaspora macrobrachium to this new genus and reclassify it as Paospora macrobrachium comb. nov.
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We combined a CRISPR/Cas12a system with a hybridization chain reaction (HCR) to develop an ultrasensitive magnetic relaxation switching (MRS) biosensor for detecting viable Salmonella typhimurium (S. typhimurium). Magnetic nanoparticles of two sizes (30 and 1000 nm: MNP30 and MNP1000, respectively) were coupled through HCR. The S. typhimurium gene-activated CRISPR/Cas12a system released MNP30 from the MNP1000-HCR-MNP30 complex through a trans-cleavage reaction. After magnetic separation, released MNP30 was collected from the supernatant and served as a transverse relaxation time (T2) signal probe. Quantitative detection of S. typhimurium is achieved by establishing a linear relationship between the change in T2 and the target gene. The biosensor's limit of detection was 77 CFU/mL (LOD = 3S/M, S = 22.30, M = 0.87), and the linear range was 102-108 CFU/mL. The accuracy for detecting S. typhimurium in real samples is comparable to that of qPCR. Thus, this is a promising method for the rapid and effective detection of foodborne pathogens.
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Introduction: Porcine deltacoronavirus (PDCoV) is a zoonotic pathogen with a global distribution, capable of infecting both pigs and humans. To mitigate the risk of cross-species transmission and potential outbreaks, it is crucial to characterize novel antiviral genes, particularly those from human hosts. Methods: This research used HIEC-6 to investigate PDCoV infection. HIEC-6 cells were infected with PDCoV. Samples were collected 48 h postinfection for proteomic analysis. Results: We discovered differential expression of MRPS6 gene at 48 h postinfection with PDCoV in HIEC-6 cells. The gene expression initially increased but then decreased. To further explore the role of MRPS6 in PDCoV infection, we conducted experiments involving the overexpression and knockdown of this gene in HIEC-6 and Caco2 cells, respectively. Our findings revealed that overexpression of MRPS6 significantly inhibited PDCoV infection in HIEC-6 cells, while knockdown of MRPS6 in Caco2 cells led to a significant increase of virus titer. Furthermore, we investigated the correlation between PDCoV infection and the expression of MRPS6. Subsequent investigations demonstrated that MRPS6 exerted an augmentative effect on the production of IFN-ß through interferon pathway activation, consequently impeding the progression of PDCoV infection in cellular systems. In conclusion, this study utilized proteomic analysis to investigate the differential protein expression in PDCoV-infected HIEC-6 cells, providing evidence for the first time that the MRPS6 gene plays a restrictive role in PDCoV virus infection. Discussion: Our findings initially provide the validation of MRPS6 as an upstream component of IFN-ß pathway, in the promotion of IRF3, IRF7, STAT1, STAT2 and IFN-ß production of HIEC-6 via dual-activation from interferon pathway.
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Deltacoronavirus , Humanos , Animales , Porcinos , Deltacoronavirus/fisiología , Deltacoronavirus/genética , Células CACO-2 , Infecciones por Coronavirus/virología , Infecciones por Coronavirus/inmunología , Línea Celular , Interacciones Huésped-Patógeno/inmunología , Proteómica/métodos , Transducción de Señal , Enfermedades de los Porcinos/virología , Enfermedades de los Porcinos/inmunologíaRESUMEN
Colloidal quantum dot (CQD) infrared (IR) photodetectors can be fabricated and operated with larger spectral tunability, fewer limitations in terms of cooling requirements and substrate lattice matching, and at a potentially lower cost than detectors based on traditional bulk materials. Silver selenide (Ag2Se) has emerged as a promising sustainable alternative to current state-of-the-art toxic semiconductors based on lead, cadmium, and mercury operating in the IR. However, an impeding gap in available absorption bandwidth for Ag2Se CQDs exists in the short-wave infrared (SWIR) region due to degenerate doping by the environment, switching the CQDs from intrinsic interband semiconductors in the near-infrared (NIR) to intraband absorbing CQDs in the mid-wave infrared (MWIR). Herein, we show that the small molecular p-type dopant 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4-TCNQ) can be used to extract electrons from the 1Se state of MWIR active Ag2Se CQDs to activate their intrinsic energy gap in the SWIR window. We demonstrate quenching of the MWIR Ag2Se absorbance peak, shifting of nitrile vibrational peaks characteristic of charge-neutral F4-TCNQ, as well as enhanced CQD absorption around â¼2500 nm after doping both in ambient and under air-free conditions. We elucidate the doping mechanism to be one that involves an integer charge transfer akin to doping in semiconducting polymers. These indications of charge transfer are promising milestones on the path to achieving sustainable SWIR Ag2Se CQD photodetectors.
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Nipah virus (NiV) is a highly lethal zoonotic virus with a potential large-scale outbreak, which poses a great threat to world health and security. In order to explore more potential factors associated with NiV, a proximity labeling method was applied to investigate the F, G, and host protein interactions systematically. We screened 1996 and 1524 high-confidence host proteins that interacted with the NiV fusion (F) glycoprotein and attachment (G) glycoprotein in HEK293T cells by proximity labeling technology, and 863 of them interacted with both F and G. The results of GO and KEGG enrichment analysis showed that most of these host proteins were involved in cellular processes, molecular binding, endocytosis, tight junction, and other functions. Cytoscape software (v3.9.1) was used for visual analysis, and the results showed that Cortactin (CTTN), Serpine mRNA binding protein 1 (SERBP1), and stathmin 1 (STMN1) were the top 20 proteins and interacted with F and G, and were selected for further validation. We observed colocalization of F-CTTN, F-SERBP1, F-STMN1, G-CTTN, G-SERBP1, and G-STMN1 using confocal fluorescence microscopy, and the results showed that CTTN, SERBP1, and STMN1 overlapped with NiV F and NiV G in HEK293T cells. Further studies found that CTTN can significantly inhibit the infection of the Nipah pseudovirus (NiVpv) into host cells, while SERBP1 and STMN1 had no significant effect on pseudovirus infection. In addition, CTTN can also inhibit the infection of the Hendra pseudovirus (HeVpv) in 293T cells. In summary, this study revealed that the potential host proteins interacted with NiV F and G and demonstrated that CTTN could inhibit NiVpv and HeVpv infection, providing new evidence and targets for the study of drugs against these diseases.
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Virus Nipah , Humanos , Cortactina , Células HEK293 , Endocitosis , GlicoproteínasRESUMEN
OBJECTIVES: Patients in cognitive behavioural therapy (CBT) who are high in interpersonal sensitivity may have difficulty fully engaging in treatment because therapy sessions require intimate interpersonal interactions that are especially uncomfortable for these individuals. The current study tests the hypotheses that patients who are high in interpersonal sensitivity benefit less from CBT for symptoms of depression and anxiety, show a slower rate of change in those symptoms, and are more likely to drop out of treatment. METHODS: Participants were 832 outpatients who received naturalistic CBT. We assessed interpersonal sensitivity before treatment began and depression and anxiety symptoms at every therapy session. We assessed early, premature, and uncollaborative termination after treatment ended. We constructed multilevel linear regression models and logistic regression models to assess the effects of baseline interpersonal sensitivity on the treatment outcome, the slope of change in depression and anxiety symptoms, and each type of dropout. RESULTS: Higher baseline interpersonal sensitivity was associated with a slower rate of change and less overall change in anxiety but not depressive symptoms. Baseline interpersonal sensitivity was not a predictor of dropout. CONCLUSIONS: Interpersonal sensitivity at baseline predicts less change and a slower rate of change in anxiety symptoms. Early detection of elevated interpersonal sensitivity can help therapists take action to address these barriers to successful treatment and help scientists build decision support tools that accurately predict the trajectory of change in anxiety symptoms for these patients.
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Terapia Cognitivo-Conductual , Relaciones Interpersonales , Humanos , Terapia Cognitivo-Conductual/métodos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Ansiedad/terapia , Ansiedad/psicología , Depresión/terapia , Depresión/psicología , Trastornos de Ansiedad/terapia , Trastornos de Ansiedad/psicología , Resultado del Tratamiento , Adulto Joven , Pacientes Desistentes del Tratamiento/psicología , Pacientes Desistentes del Tratamiento/estadística & datos numéricosRESUMEN
Porcine Deltacoronavirus (PDCoV) is a newly identified coronavirus that causes severe intestinal lesions in piglets. However, the understanding of how PDCoV interacts with human hosts is limited. In this study, we aimed to investigate the interactions between PDCoV and human intestinal cells (HIEC-6) by analyzing the transcriptome at different time points post-infection (12 h, 24 h, 48 h). Differential gene analysis revealed a total of 3560, 5193, and 4147 differentially expressed genes (DEGs) at 12 h, 24 h, and 48 h, respectively. The common genes among the DEGs at all three time points were enriched in biological processes related to cytokine production, extracellular matrix, and cytokine activity. KEGG pathway analysis showed enrichment of genes involved in the p53 signaling pathway, PI3K-Akt signaling pathway, and TNF signaling pathway. Further analysis of highly expressed genes among the DEGs identified significant changes in the expression levels of BUB1, DDIT4, ATF3, GBP2, and IRF1. Comparison of transcriptome data at 24 h with other time points revealed 298 DEGs out of a total of 6276 genes. KEGG analysis of these DEGs showed significant enrichment of pathways related to viral infection, specifically the PI3K-Akt and P38 MAPK pathways. Furthermore, the genes EFNA1 and KITLG, which are associated with viral infection, were found in both enriched pathways, suggesting their potential as therapeutic or preventive targets for PDCoV infection. The enhancement of PDCoV infection in HIEC-6 was observed upon inhibition of the PI3K-Akt and P38 MAPK signaling pathways using sophoridine. Overall, these findings contribute to our understanding of the molecular mechanisms underlying PDCoV infection in HIEC-6 cells and provide insights for developing preventive and therapeutic strategies against PDCoV infection.
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Perfilación de la Expresión Génica , Transducción de Señal , Transcriptoma , Animales , Humanos , Línea Celular , Infecciones por Coronavirus/virología , Infecciones por Coronavirus/genética , Deltacoronavirus/genética , Interacciones Huésped-Patógeno/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Porcinos , Enfermedades de los Porcinos/virología , Enfermedades de los Porcinos/genéticaRESUMEN
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne hemorrhagic fever disease with high fatality rate of 10%-20%. Vaccines or specific therapeutic measures remain lacking. Human interferon inducible transmembrane protein 3 (hIFITM3) is a broad-spectrum antiviral factor targeting viral entry. However, the antiviral activity of hIFITM3 against SFTS virus (SFTSV) and the functional mechanism of IFITM3 remains unclear. Here we demonstrate that endogenous IFITM3 provides protection against SFTSV infection and participates in the anti-SFTSV effect of type â and â ¢ interferons (IFNs). IFITM3 overexpression exhibits anti-SFTSV function by blocking Gn/Gc-mediated viral entry and fusion. Further studies showed that IFITM3 binds SFTSV Gc directly and its intramembrane domain (IMD) is responsible for this interaction and restriction of SFTSV entry. Mutation of two neighboring cysteines on IMD weakens IFITM3-Gc interaction and attenuates the antiviral activity of IFITM3, suggesting that IFITM3-Gc interaction may partly mediate the inhibition of SFTSV entry. Overall, our data demonstrate for the first time that hIFITM3 plays a critical role in the IFNs-mediated anti-SFTSV response, and uncover a novel mechanism of IFITM3 restriction of SFTSV infection, highlighting the potential of clinical intervention on SFTS disease.
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Factores de Restricción Antivirales , Infecciones por Bunyaviridae , Síndrome de Trombocitopenia Febril Grave , Humanos , Infecciones por Bunyaviridae/inmunología , Proteínas de la Membrana/inmunología , Phlebovirus , Proteínas de Unión al ARN/inmunología , Síndrome de Trombocitopenia Febril Grave/inmunología , Proteínas Virales/metabolismo , Internalización del Virus , Factores de Restricción Antivirales/inmunologíaRESUMEN
IMPORTANCE: Rotavirus (RV) is an important zoonosis virus, which can cause severe diarrhea and extra-intestinal infection. To date, some proteins or carbohydrates have been shown to participate in the attachment or internalization of RV, including HGBAs, Hsc70, and integrins. This study attempted to indicate whether there were other proteins that would participate in the entry of RV; thus, the RV VP4-interacting proteins were identified by proximity labeling. After analysis and verification, it was found that VIM and ACTR2 could significantly promote the proliferation of RV in intestinal cells. Through further viral binding assays after knockdown, antibody blocking, and recombinant protein overexpression, it was revealed that both VIM and ACTR2 could promote RV replication.
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Proteína 2 Relacionada con la Actina , Proteínas de la Cápside , Mapas de Interacción de Proteínas , Rotavirus , Vimentina , Animales , Humanos , Proteína 2 Relacionada con la Actina/genética , Proteína 2 Relacionada con la Actina/metabolismo , Proteínas de la Cápside/metabolismo , Intestinos/citología , Rotavirus/química , Rotavirus/metabolismo , Vimentina/genética , Vimentina/metabolismo , Internalización del Virus , Replicación Viral , Unión ProteicaRESUMEN
The severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne human-infecting bunyavirus, which utilizes two envelope glycoproteins, Gn and Gc, to enter host cells. However, the structure and organization of these glycoproteins on virion surface are not yet known. Here we describe the structure of SFTSV determined by single particle reconstruction, which allows mechanistic insights into bunyavirus assembly at near-atomic resolution. The SFTSV Gn and Gc proteins exist as heterodimers and further assemble into pentameric and hexameric peplomers, shielding the Gc fusion loops by both intra- and inter-heterodimer interactions. Individual peplomers are associated mainly through the ectodomains, in which the highly conserved glycans on N914 of Gc play a crucial role. This elaborate assembly stabilizes Gc in the metastable prefusion conformation and creates some cryptic epitopes that are only accessible in the intermediate states during virus entry. These findings provide an important basis for developing vaccines and therapeutic drugs.
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Orthobunyavirus , Phlebovirus , Síndrome de Trombocitopenia Febril Grave , Humanos , Proteínas del Envoltorio Viral/metabolismo , Microscopía por Crioelectrón , Glicoproteínas/metabolismoRESUMEN
Avipoxvirus 282E4 strain was extensively applied into recombinant vaccine vector to prevent other infectious diseases. However, little information on the genomic background, functional and genetic evolutionary of the isolate 282E4 strain was clarified. The results showed that the linear genome of avipoxvirus 282E4 was 308,826 bp, containing 313 open reading frames (ORFs) and 12 new predicted ORFs. The 282E4 strain appears to encode two novel thymidine kinase proteins and two TGF-beta-like proteins that may be associated with the suppression of the host's antiviral response. Avipoxvirus 282E4 also encodes 57 ankyrin repeat proteins and 5 variola B22R-like proteins, which composed 7% of the avipoxvirus 282E4 genome. GO and KEGG analysis further revealed that 12 ORFs participate in viral transcription process, 7 ORFs may function during DNA repair, replication and biological synthesis, and ORF 208 is involved in the process of virus life cycle. Interestingly, phylogenetic analysis based on concatenated sequences p4b and DNA polymerase of avipoxviruses gene demonstrates that avipoxvirus 282E4 strain is divergent from known FWPV isolates and is similar to shearwater poxvirus (SWPV-1) that belongs to the CNPV-like virus. Sequencing avipoxvirus 282E4 is a significant step to judge the genetic position of avipoxviruses within the larger Poxviridae phylogenetic tree and provide a new insight into the genetic background of avipoxvirus 282E4 and interspecies transmission of poxviruses, meanwhile, explanation of gene function provides theoretical foundation for vaccine design with 282E4 strain as skeleton.
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Non-alcoholic steatohepatitis (NASH) is one of the most prevalent diseases worldwide; it is characterized by hepatic lipid accumulation, inflammation, and progressive fibrosis. Here, a Western diet combined with low-dose weekly carbon tetrachloride was fed to C57BL/6J mice for 12 weeks to build a NASH model to investigate the attenuating effects and possible mechanisms of Lactiplantibacillus plantarum LPJZ-658. Hepatic pathology, lipid profiles, and gene expression were assessed. The metabolomic profiling of the serum was performed. The composition structure of gut microbiota was profiled using 16s rRNA sequencing. The results show that LPJZ-658 treatment significantly attenuated liver injury, steatosis, fibrosis, and inflammation in NASH mice. Metabolic pathway analysis revealed that several pathways, such as purine metabolism, glycerophospholipid metabolism, linoleic acid metabolism, and primary bile acid biosynthesis, were associated with NASH. Notably, we found that treatment with LPJZ-658 regulated the levels of bile acids (BAs) in the serum. Moreover, LPJZ-658 restored NASH-induced gut microbiota dysbiosis. The correlation analysis deduced obvious interactions between BAs and gut microbiota. The current study indicates that LPJZ-658 supplementation protects against NASH progression, which is accompanied by alternating BA metabolic and modulating gut microbiota.
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Microbioma Gastrointestinal , Enfermedad del Hígado Graso no Alcohólico , Animales , Ratones , Enfermedad del Hígado Graso no Alcohólico/metabolismo , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/metabolismo , Ratones Endogámicos C57BL , Hígado/metabolismo , Lípidos/farmacología , Inflamación/metabolismo , Fibrosis , Ácidos y Sales Biliares/metabolismoRESUMEN
IMPORTANCE: Emerging vaccine-breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants highlight an urgent need for novel antiviral therapies. Understanding the pathogenesis of coronaviruses is critical for developing antiviral drugs. Here, we demonstrate that the SARS-CoV-2 N protein suppresses interferon (IFN) responses by reducing early growth response gene-1 (EGR1) expression. The overexpression of EGR1 inhibits SARS-CoV-2 replication by promoting IFN-regulated antiviral protein expression, which interacts with and degrades SARS-CoV-2 N protein via the E3 ubiquitin ligase MARCH8 and the cargo receptor NDP52. The MARCH8 mutants without ubiquitin ligase activity are no longer able to degrade SARS-CoV-2 N proteins, indicating that MARCH8 degrades SARS-CoV-2 N proteins dependent on its ubiquitin ligase activity. This study found a novel immune evasion mechanism of SARS-CoV-2 utilized by the N protein, which is helpful for understanding the pathogenesis of SARS-CoV-2 and guiding the design of new prevention strategies against the emerging coronaviruses.
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Proteína 1 de la Respuesta de Crecimiento Precoz , Interacciones Microbiota-Huesped , SARS-CoV-2 , Ubiquitina-Proteína Ligasas , Replicación Viral , Humanos , COVID-19/virología , Descubrimiento de Drogas , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , SARS-CoV-2/crecimiento & desarrollo , SARS-CoV-2/patogenicidad , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinas/metabolismoRESUMEN
This study aimed to investigate the effects of L. plantarum LPJZ-658 on the production, meat quality, intestinal morphology, and cecal microbiota of broilers. White-feathered broilers (1 day old, n = 600) were randomly assigned to two groups and raised for six weeks. The individuals in the LPJZ-658 group were supplemented with 2.6 × 109 cfu/g LPJZ-658. The growth performance, meat quality, intestinal epithelium morphology, and cecal microbiota were observed. The results showed that the average daily gain, average daily feed intake, and feed conversion ratio of broilers in the LPJZ-658 group were significantly improved. In addition, the LPJZ-658 groups had a higher thigh muscle (TM) yield, TM color, TMpH24h, breast muscle (BM) pH24h, and BM color24h, while the BM cooking loss was significantly lower than the CON group. Moreover, supplementation with LPJZ-658 increased ileum and cecum length, duodenum and ileum villus height, and ileum villus height/crypt depth ratio. Furthermore, 16S rRNA sequencing revealed the dietary LPJZ-658 supplementation modulated the diversity and composition of cecal microflora. At the phylum level, the relative abundances of Proteobacteria, Actinobacteria, Verrucomicrobiota, and Acidobacteriota were significantly higher. In addition, LPJZ-658 substantially decreased the genus relative abundances of Streptococcus, Veillonella, Neisseria, and Haemophilus compared with the CON group and facilitated the growth and colonization of beneficial cecal bacteria, such as OBacteroides, Phascolarctobacterium, Bacillus, and Akkermansia. It was concluded that LPJZ-658 supplementation significantly increased growth production, improved meat quality and intestinal status, and modulated the intestinal microbiota in the broilers.
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Deoxynivalenol is one of the most widely distributed mycotoxins in cereals and poses tremendous threats to the agricultural environment and public health. Therefore, it is particularly important to develop sensitive and interference-resistant deoxynivalenol analysis methods. Here, we establish a "Lollipop" particle counting immunoassay (LPCI) based on antigen-powered CRISPR-Cas12a dual signal amplification. LPCI achieves high sensitivity and accuracy through antigen-powered CRISPR-Cas dual signal amplification combined with particle counting immunoassay. This strategy not only broadens the applicability of the CRISPR-Cas system in the field of non-nucleic acid target detection; it also improves the sensitivity of particle counting immunoassay. The introduction of a polystyrene "lollipop" immunoassay carrier further enables efficiently simultaneous pre-treatment of multiple samples and overcomes complex matrix interference in real samples. The linear detection range of LPCI for deoxynivalenol was 0.1-500 ng/mL with a detection limit of 0.061 ng/mL. The platform greatly broadens the scope of the CRISPR-Cas sensor for the detection of non-nucleic acid hazards in the environment and food samples.
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Técnicas Biosensibles , Sistemas CRISPR-Cas , Agricultura , Grano Comestible , Inmunoensayo , Técnicas de Amplificación de Ácido NucleicoRESUMEN
Type III interferons (IFNLs) have critical roles in the host's innate immune system, also serving as the first line against pathogenic infections of mucosal surfaces. In mammals, several IFNLs have been reported; however, only limited data on the repertoire of IFNLs in avian species is available. Previous studies showed only one member in chicken (chIFNL3). Herein, we identified a novel chicken IFNL for the first time, termed chIFNL3a, which contains 354 bp, and encodes 118 amino acids. The predicted protein is 57.1% amino acid identity with chIFNL. Genetic, evolutionary, and sequence analyses indicated that the new open reading frame (ORF) groups with type III chicken IFNs represent a novel splice variant. Compared to IFNs from different species, the new ORF is clustered within the type III IFNs group. Further study showed that chIFNL3a could activate a panel of IFN-regulated genes and function mediated by the IFNL receptor, and chIFNL3a markedly inhibited the replication of Newcastle disease virus (NDV) and influenza virus in vitro. These data collectively shed light on the repertoire of IFNs in avian species and provide useful information that further elucidate the interaction of the chIFNLs and viral infection of poultry. IMPORTANCE Interferons (IFNs) are critical soluble factors in the immune system, and are composed of 3 types (I, II, and III) that utilize different receptor complexes (IFN-αR1/IFN-αR2, IFN-γR1/IFN-γR2, and IFN-λR1/IL-10R2, respectively). Herein, we identified IFNL from the genomic sequences of chicken and termed it chIFNL3a, located on chromosome 7 of chicken. Phylogenetically clustered with all known types of chicken IFNs, the finding of this IFN is considered a type III IFN. To further evaluate the biological properties of chIFNL3a, the target protein was prepared by the baculovirus expression system (BES), which could markedly inhibit the replication of NDV and influenza viruses. In this study, we uncovered a new interferon lambda splice variant of chicken, termed chIFNL3a, which could inhibit viral replication in cells. Importantly, these novel findings may extend to other viruses, offering a new direction for therapeutic interventions.
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Pollos , Orthomyxoviridae , Animales , Interferón lambda , Antivirales/farmacología , Interferones/metabolismo , Orthomyxoviridae/metabolismo , Virus de la Enfermedad de Newcastle/metabolismo , MamíferosRESUMEN
Using scanning transmission electron microscopy, along with electron energy loss spectroscopy, under cryogenic conditions, we demonstrate transition-metal dissolution from a layered Ni-rich oxide cathode material and subsequent diffusion into the bulk of a lithium thiophosphate solid electrolyte during electrochemical cycling. This problem has previously only been considered for liquid-electrolyte-based batteries.
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The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a severe global health crisis; its structural protein envelope (E) is critical for viral entry, budding, production, and induction of pathology which makes it a potential target for therapeutics against COVID-19. Here, we find that the E3 ligase RNF5 interacts with and catalyzes ubiquitination of E on the 63rd lysine, leading to its degradation by the ubiquitin-proteasome system (UPS). Importantly, RNF5-induced degradation of E inhibits SARS-CoV-2 replication and the RNF5 pharmacological activator Analog-1 alleviates disease development in a mouse infection model. We also found that RNF5 is distinctively expressed in different age groups and in patients displaying different disease severity, which may be exploited as a prognostic marker for COVID-19. Furthermore, RNF5 recognized the E protein from various SARS-CoV-2 strains and SARS-CoV, suggesting that targeting RNF5 is a broad-spectrum antiviral strategy. Our findings provide novel insights into the role of UPS in antagonizing SARS-CoV-2 replication, which opens new avenues for therapeutic intervention to combat the COVID-19 pandemic.
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COVID-19 , Ubiquitina-Proteína Ligasas , Animales , Ratones , Humanos , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , SARS-CoV-2/metabolismo , COVID-19/genética , Pandemias , Antivirales/farmacología , Antivirales/química , Ubiquitina/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas de la MembranaRESUMEN
COVID-19 has globally spread to burden the medical system. Even with a massive vaccination, a mucosal vaccine offering more comprehensive and convenient protection is imminent. Here, a micro-sized vaccine based on recombinant Lactiplantibacillus plantarum (rLP) displaying spike or receptor-binding domain (RBD) was characterized as microparticles, and its safety and protective effects against SARS-CoV-2 were evaluated. We found a 66.7% mortality reduction and 100% protection with rLP against SARS-CoV-2 in a mouse model. The histological analysis showed decreased hemorrhage symptoms and increased leukocyte infiltration in the lung. Especially, rLP:RBD significantly decreased pulmonary viral loads. For the first time, our study provides a Lactiplantibacillus plantarum-vectored vaccine to prevent COVID-19 progress and transmission via intranasal vaccination.