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Metabolism in host cells can be modulated after viral infection, favoring viral survival or clearance. Here, we report that lipid droplet (LD) synthesis in host cells can be modulated by yin yang 1 (YY1) after porcine reproductive and respiratory syndrome virus (PRRSV) infection, resulting in active antiviral activity. As a ubiquitously distributed transcription factor, there was increased expression of YY1 upon PRRSV infection both in vitro and in vivo. YY1 silencing promoted the replication of PRRSV, whereas YY1 overexpression inhibited PRRSV replication. PRRSV infection led to a marked increase in LDs, while YY1 knockout inhibited LD synthesis, and YY1 overexpression enhanced LD accumulation, indicating that YY1 reprograms PRRSV infection-induced intracellular LD synthesis. We also showed that the viral components do not colocalize with LDs during PRRSV infection, and the effect of exogenously induced LD synthesis on PRRSV replication is nearly lethal. Moreover, we demonstrated that YY1 affects the synthesis of LDs by regulating the expression of lipid metabolism genes. YY1 negatively regulates the expression of fatty acid synthase (FASN) to weaken the fatty acid synthesis pathway and positively regulates the expression of peroxisome proliferator-activated receptor gamma (PPARγ) to promote the synthesis of LDs, thus inhibiting PRRSV replication. These novel findings indicate that YY1 plays a crucial role in regulating PRRSV replication by reprogramming LD synthesis. Therefore, our study provides a novel mechanism of host resistance to PRRSV and suggests potential new antiviral strategies against PRRSV infection.IMPORTANCEPorcine reproductive and respiratory virus (PRRSV) has caused incalculable economic damage to the global pig industry since it was first discovered in the 1980s. However, conventional vaccines do not provide satisfactory protection. It is well known that viruses are parasitic pathogens, and the completion of their replication life cycle is highly dependent on host cells. A better understanding of host resistance to PRRSV infection is essential for developing safe and effective strategies to control PRRSV. Here, we report a crucial host antiviral molecule, yin yang 1 (YY1), which is induced to be expressed upon PRRSV infection and subsequently inhibits virus replication by reprogramming lipid droplet (LD) synthesis through transcriptional regulation. Our work provides a novel antiviral mechanism against PRRSV infection and suggests that targeting YY1 could be a new strategy for controlling PRRSV.
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Gotas Lipídicas , Virus del Síndrome Respiratorio y Reproductivo Porcino , Replicación Viral , Factor de Transcripción YY1 , Factor de Transcripción YY1/metabolismo , Factor de Transcripción YY1/genética , Animales , Virus del Síndrome Respiratorio y Reproductivo Porcino/fisiología , Virus del Síndrome Respiratorio y Reproductivo Porcino/genética , Porcinos , Gotas Lipídicas/metabolismo , Síndrome Respiratorio y de la Reproducción Porcina/virología , Síndrome Respiratorio y de la Reproducción Porcina/metabolismo , Síndrome Respiratorio y de la Reproducción Porcina/genética , Línea Celular , Metabolismo de los Lípidos , Interacciones Huésped-PatógenoRESUMEN
A 2 × 2 switch based on differential effective thermo-optic (TO) coefficients of waveguide supermodes is proposed and experimentally demonstrated as a more compact alternative to Mach-Zehnder interferometer (MZI)-based switches used in coherent photonic matrix processing networks. The total waveguide width of the device is 1.335â µm. Using a novel, to the best of our knowledge, supermode coupler with a wideband 3-dB coupling ratio, the switch was engineered to have on-off extinction ratios (ERs) ranging from 24.1 to 38.9â dB for the two output ports over a 135â nm bandwidth. Insertion losses (ILs) of less than 0.3 and 0.4â dB over the 100â nm bandwidth were measured for bar and cross transmission, respectively. The waveguide width error tolerance is +/-30â nm. The proposed device has the potential to improve the scalability of a programmable coherent mesh for matrix processing by increasing the integration density without sacrificing the overall accuracy or limiting the operational wavelength range of the mesh.
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Porcine circovirus type 2 (PCV2) is intensely prevalent in global pig farms. The PCV2 vaccine is an important means of preventing and controlling PCV2. The quality control of PCV2 vaccines is predominantly based on detection techniques such as animal testing and neutralizing antibody titration. Measuring the content of effective proteins in vaccines to measure vaccine efficacy is an excellent alternative to traditional methods, which can greatly accelerate the development speed and testing time of vaccines. In this study, we screened a monoclonal antibody (mAb) that can effectively recognize not only the exogenous expression of PCV2 Cap protein but also PCV2 virus. The double antibody sandwich ELISA (DAS-ELISA) was developed using this mAb that specifically recognize PCV2 Cap. The minimum protein content detected by this method is 3.5â¯ng/mL. This method can be used for the quality control of PCV2 inactivated vaccine and subunit vaccine, and the detection results are consistent with the results of mice animal experiments. This method has the advantages of simple operation, good sensitivity, high specificity and wide application. It can detect the effective antigen Cap protein content of various types of PCV2 vaccines, which not only shorten the vaccine inspection time but also save costs.
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Anticuerpos Monoclonales , Anticuerpos Antivirales , Antígenos Virales , Infecciones por Circoviridae , Circovirus , Ensayo de Inmunoadsorción Enzimática , Sensibilidad y Especificidad , Enfermedades de los Porcinos , Vacunas Virales , Circovirus/inmunología , Animales , Ensayo de Inmunoadsorción Enzimática/métodos , Porcinos , Vacunas Virales/inmunología , Anticuerpos Monoclonales/inmunología , Antígenos Virales/inmunología , Antígenos Virales/análisis , Ratones , Anticuerpos Antivirales/sangre , Infecciones por Circoviridae/veterinaria , Infecciones por Circoviridae/diagnóstico , Infecciones por Circoviridae/prevención & control , Enfermedades de los Porcinos/diagnóstico , Enfermedades de los Porcinos/prevención & control , Enfermedades de los Porcinos/virología , Proteínas de la Cápside/inmunologíaRESUMEN
Porcine reproductive and respiratory syndrome virus is one of the main pathogens threatening the global pig industry, and there is still a lack of effective therapeutic drugs. Sanggenon C is a flavanone Diels-Alder adduct compound extracted from the root bark of the mulberry genus, which has blood pressure-reducing, anti-atherosclerotic, anti-oxidative, and anti-inflammatory effects. In our previous study, Sanggenon C was confirmed to significantly inhibit PRRSV replication in vitro. However, its antiviral potential to inhibit PRRSV infection in vivo has not been evaluated in piglets. Here, the antiviral effect of Sanggenon C was evaluated in PRRSV-challenged piglets based on assessments of rectal temperature, viral load, pathological changes of lung tissue and secretion of inflammatory cytokines. The results showed that Sanggenon C treatment relieved the clinical symptoms, reduced the viral loads in the lungs and bloods, alleviated the pathological damage of lung tissue, decreased the secretion of inflammatory cytokines, and shorten the excretion time of virus from the oral and nasal secretions and feces of piglets after PRRSV infection. The results indicated that Sanggenon C is a promising anti-PRRSV drug, which provides a new strategy for the prevention and control of PRRS in clinical practice.
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Benzofuranos , Cromonas , Síndrome Respiratorio y de la Reproducción Porcina , Virus del Síndrome Respiratorio y Reproductivo Porcino , Enfermedades de los Porcinos , Animales , Porcinos , Síndrome Respiratorio y de la Reproducción Porcina/tratamiento farmacológico , Síndrome Respiratorio y de la Reproducción Porcina/prevención & control , Citocinas , Antivirales/farmacología , Antivirales/uso terapéutico , Replicación Viral , Enfermedades de los Porcinos/patologíaRESUMEN
Low-dimensional platinum diselenide (PtSe2) is a promising candidate for high-performance optoelectronics in the short-wavelength mid-infrared band due to its high carrier mobility, excellent stability, and tunable bandgap. However, light usually interacts moderately with low-dimensional PtSe2, limiting the optoelectronic responses of PtSe2-based devices. Here we demonstrated a giant optical absorption of a PtSe2-on-silicon waveguide by integrating a ten-layer PtSe2 film on an ultra-thin silicon waveguide. The weak mode confinement in the ultra-thin waveguide dramatically increases the waveguide mode overlap with the PtSe2 film. Our experimental results show that the absorption coefficient of the PtSe2-on-silicon waveguide is in the range of 0.0648 dB µm-1 to 0.0704 dB µm-1 in a spectral region of 2200 nm to 2300 nm wavelengths. Furthermore, we also studied the optical absorption in an ultra-thin silicon microring resonator. Our study provides a promising approach to developing PtSe2-on-silicon hybrid optoelectronic integrated circuits.
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Porcine reproductive and respiratory syndrome (PRRS) is a serious infectious disease and one of the major causes of death in the global pig industry. PRRS virus (PRRSV) strains have complex and diverse genetic characteristics and cross-protection between strains is low, which complicates vaccine selection; thus, the current vaccination strategy has been greatly compromised. Therefore, it is necessary to identify effective natural compounds for the clinical treatment of PRRS. A small molecule library composed of 720 natural compounds was screened in vitro, and we found that Sanggenon C (SC) was amongst the most effective natural compound inhibitors of PRRSV infection. Compared with ribavirin, SC more significantly inhibited PRRSV infection at both the gene and protein levels and reduced the viral titres and levels of protein expression and inflammatory cytokine secretion to more effectively protect cells from PRRSV infection and damage. Mechanistically, SC inhibits activation of the NF-κB signalling pathway by promoting TRAF2 expression, thereby reducing PRRSV replication. In conclusion, by screening natural compounds, we found that SC suppresses PRRSV infection by regulating the TRAF2/NF-κB signalling pathway. This study contributes to a deeper understanding of the therapeutic targets and pathogenesis of PRRSV infection. More importantly, our results demonstrate that SC has potential as a candidate for the treatment of PRRS.
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Síndrome Respiratorio y de la Reproducción Porcina , Virus del Síndrome Respiratorio y Reproductivo Porcino , Enfermedades de los Porcinos , Porcinos , Animales , FN-kappa B/metabolismo , Virus del Síndrome Respiratorio y Reproductivo Porcino/metabolismo , Síndrome Respiratorio y de la Reproducción Porcina/tratamiento farmacológico , Síndrome Respiratorio y de la Reproducción Porcina/prevención & control , Factor 2 Asociado a Receptor de TNF/metabolismo , Línea Celular , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
The global coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the greatest worldwide public health threat of this century, which may predispose multi-organ failure (especially the lung) and death despite numerous mild and moderate symptoms. Recent studies have unraveled the molecular and clinical characteristics of the infectivity, pathogenicity, and immune evasion of SARS-CoV-2 and thus improved the development of many different therapeutic strategies to combat COVID-19, including treatment and prevention. Previous studies have indicated that nitric oxide (NO) is an antimicrobial and anti-inflammatory molecule with key roles in pulmonary vascular function in the context of viral infections and other pulmonary disease states. This review summarized the recent advances of the pathogenesis of SARS-CoV-2, and accordingly elaborated on the potential application of NO in the management of patients with COVID-19 through antiviral activities and anti-inflammatory properties, which mitigate the propagation of this disease. Although there are some limits of NO in the treatment of COVID-19, it might be a worthy candidate in the multiple stages of COVID-19 prevention or therapy.
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COVID-19 , Humanos , SARS-CoV-2 , Óxido Nítrico , Antivirales/farmacología , Antivirales/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéuticoRESUMEN
Porcine epidemic diarrhea virus (PEDV) leads to enormous economic losses for the pork industry. However, the commercial vaccines failed to fully protect against the epidemic strains. Previously, the rCH/SX/2016-SHNXP strain with the entire E protein and the rCH/SX/2015 strain with the deletion of 7-amino-acid (7-aa) at positions 23-29 in E protein were constructed and rescued. The pathogenicity assay indicated that rCH/SX/2015 is an attenuated strain, but rCH/SX/2016-SHNXP belongs to the virulent strains. Then, the recombination PEDV (rPEDV-EΔaa23-aa29)strain with a 7-aa deletion in the E protein was generated, using the highly virulent rCH/SX/2016-SHNXP strain (rPEDV-Ewt) as the backbone. Compared with the rPEDV-Ewt strain, the release and infectivity of the rPEDV-EΔaa23-aa29 strain were significantly reduced in vitro, but stronger interferon (IFN) responses were triggered both in vitro and in vivo. The pathogenicity assay showed that the parental strain resulted in severe diarrhea (100%) and death (100%) in all piglets. Compared with the parental strain group, rPEDV-EΔaa23-aa29 caused lower mortality (33%) and diminished fecal PEDV RNA shedding. At 21 days, all surviving pigs were challenged orally with rPEDV-Ewt. No pigs died in the two groups. Compared with the mock group, significantly delayed and milder diarrhea and reduced fecal PEDV RNA shedding were detected in the rPEDV-EΔaa23-aa29 group. In conclusion, the deletion of a 7-aa fragment in the E protein (EΔaa23-aa29) attenuated PEDV but retained its immunogenicity, which can offer new ideas for the design of live attenuated vaccines and provide new insights into the attenuated mechanism of PEDV. IMPORTANCE Porcine epidemic diarrhea virus (PEDV) causes high mortality in neonatal piglets and remains a large challenge to the pork industry. Unfortunately, no safe and effective vaccines are available yet. The pathogenesis and molecular basis of the attenuation of PEDV remain unclear, which seriously hinders the development of PEDV vaccines. This study found that the rPEDV carrying EΔaa23-aa29 mutation in the E protein induced significantly higher IFN responses than the parental virus, partially attenuated, and remained immunogenic in piglets. For the first time, PEDV E was verified as an IFN antagonist in the infection context and identified as a virulence factor of PEDV. Our data also suggested that EΔaa23-aa29 mutation can be a good target for the development of live attenuated vaccines for PEDV and also provide new perspectives for the attenuated mechanism of PEDV.
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Infecciones por Coronavirus , Virus de la Diarrea Epidémica Porcina , Enfermedades de los Porcinos , Proteínas del Envoltorio Viral , Animales , Infecciones por Coronavirus/veterinaria , Interferones , Virus de la Diarrea Epidémica Porcina/genética , Virus de la Diarrea Epidémica Porcina/fisiología , ARN , Porcinos , Enfermedades de los Porcinos/inmunología , Enfermedades de los Porcinos/virología , Vacunas Atenuadas/genética , Eliminación de Secuencia , Proteínas del Envoltorio Viral/genéticaRESUMEN
Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant diseases affecting the pig industry worldwide. The PRRSV mutation rate is the highest among the RNA viruses. To date, NADC30-like PRRSV and highly pathogenic PRRSV (HP-PRRSV) are the dominant epidemic strains in China; however, commercial vaccines do not always provide sufficient cross-protection, and the reasons for insufficient protection are unclear. This study isolated a wild-type NADC30-like PRRSV, SX-YL1806, from Shaanxi Province. Vaccination challenge experiments in piglets showed that commercial modified live virus (MLV) vaccines provided good protection against HP-PRRSV. However, it could not provide sufficient protection against the novel strain SX-YL1806. To explore the reasons for this phenomenon, we compared the genomic homology between the MLV strain and HP-PRRSV or NADC30-like PRRSV and found that the MLV strain had a lower genome similarity with NADC30-like PRRSV. Serum neutralization assay showed that MLV-immune serum slightly promoted the homologous HP-PRRSV replication and significantly promoted the heterologous NADC30-like PRRSV strain replication in vitro, suggesting that antibody-dependent enhancement (ADE) might also play a role in decreasing MLV protective efficacy. These findings expand our understanding of the potential factors affecting the protective effect of PRRSV MLV vaccines against the NADC30-like strains.
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Síndrome Respiratorio y de la Reproducción Porcina , Virus del Síndrome Respiratorio y Reproductivo Porcino , Vacunas Virales , Animales , Porcinos , Virus del Síndrome Respiratorio y Reproductivo Porcino/genética , Acrecentamiento Dependiente de Anticuerpo , Síndrome Respiratorio y de la Reproducción Porcina/prevención & control , Genoma Viral , Vacunas Atenuadas/genética , Genómica , Vacunas Virales/genéticaRESUMEN
Despite the increasing impact of atmospheric nitrogen (N) deposition on terrestrial greenhouse gas (GHG) budget, through driving both the net atmospheric CO2 exchange and the emission or uptake of non-CO2 GHGs (CH4 and N2 O), few studies have assessed the climatic impact of forests and grasslands under N deposition globally based on different bottom-up approaches. Here, we quantify the effects of N deposition on biomass C increment, soil organic C (SOC), CH4 and N2 O fluxes and, ultimately, the net ecosystem GHG balance of forests and grasslands using a global comprehensive dataset. We showed that N addition significantly increased plant C uptake (net primary production) in forests and grasslands, to a larger extent for the aboveground C (aboveground net primary production), whereas it only caused a small or insignificant enhancement of SOC pool in both upland systems. Nitrogen addition had no significant effect on soil heterotrophic respiration (RH ) in both forests and grasslands, while a significant N-induced increase in soil CO2 fluxes (RS , soil respiration) was observed in grasslands. Nitrogen addition significantly stimulated soil N2 O fluxes in forests (76%), to a larger extent in grasslands (87%), but showed a consistent trend to decrease soil uptake of CH4 , suggesting a declined sink capacity of forests and grasslands for atmospheric CH4 under N enrichment. Overall, the net GHG balance estimated by the net ecosystem production-based method (forest, 1.28 Pg CO2 -eq year-1 vs. grassland, 0.58 Pg CO2 -eq year-1 ) was greater than those estimated using the SOC-based method (forest, 0.32 Pg CO2 -eq year-1 vs. grassland, 0.18 Pg CO2 -eq year-1 ) caused by N addition. Our findings revealed that the enhanced soil C sequestration by N addition in global forests and grasslands could be only marginally offset (1.5%-4.8%) by the combined effects of its stimulation of N2 O emissions together with the reduced soil uptake of CH4 .
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Gases de Efecto Invernadero , Ecosistema , Pradera , Dióxido de Carbono/análisis , Metano/análisis , Óxido Nitroso/análisis , Bosques , Suelo , NitrógenoRESUMEN
Chemokine production by epithelial cells is crucial for neutrophil recruitment to sites of inflammation during viral infection. However, the effect of chemokine on epithelia and how chemokine is involved in coronavirus infection remains to be fully understood. Here, we identified an inducible chemokine interleukin-8 (CXCL8/IL-8), which could promote coronavirus porcine epidemic diarrhea virus (PEDV) infection in African green monkey kidney epithelial cells (Vero) and Lilly Laboratories cell-porcine kidney 1 epithelial cells (LLC-PK1). IL-8 deletion restrained cytosolic calcium (Ca2+), whereas IL-8 stimulation improved cytosolic Ca2+. The consumption of Ca2+ restricted PEDV infection. PEDV internalization and budding were obvious reductions when cytosolic Ca2+ was abolished in the presence of Ca2+ chelators. Further study revealed that the upregulated cytosolic Ca2+ redistributes intracellular Ca2+. Finally, we identified that G protein-coupled receptor (GPCR)-phospholipase C (PLC)-inositol trisphosphate receptor (IP3R)-store-operated Ca2+ (SOC) signaling was crucial for enhancive cytosolic Ca2+ and PEDV infection. To our knowledge, this study is the first to uncover the function of chemokine IL-8 during coronavirus PEDV infection in epithelia. PEDV induces IL-8 expression to elevate cytosolic Ca2+, promoting its infection. Our findings reveal a novel role of IL-8 in PEDV infection and suggest that targeting IL-8 could be a new approach to controlling PEDV infection. IMPORTANCE Coronavirus porcine epidemic diarrhea virus (PEDV) is a highly contagious enteric coronavirus that caused severe economic losses worldwide, and more effort is needed to develop economical and efficient vaccines to control or eliminate this disease. The chemokine interleukin-8 (CXCL8/IL-8) is indispensable for the activation and trafficking of inflammatory mediators and tumor progression and metastasis. This study evaluated the effect of IL-8 on PEDV infection in epithelia. We found that IL-8 expression improved cytosolic Ca2+ in epithelia, facilitating PEDV rapid internalization and egress. G protein-coupled receptor (GPCR)-phospholipase C (PLC)-inositol trisphosphate receptor (IP3R)-SOC signaling was activated by IL-8, releasing the intracellular Ca2+ stores from endoplasmic reticulum (ER). These findings provide a better understanding of the role of IL-8 in PEDV-induced immune responses, which will help develop small-molecule drugs for coronavirus cure.
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Infecciones por Coronavirus , Coronavirus , Virus de la Diarrea Epidémica Porcina , Enfermedades de los Porcinos , Animales , Quimiocinas , Chlorocebus aethiops , Interleucina-8 , Virus de la Diarrea Epidémica Porcina/fisiología , Porcinos , Células Vero , Replicación ViralRESUMEN
African swine fever (ASF) is etiologically an acute, highly contagious and hemorrhagic disease caused by African swine fever virus (ASFV). Due to its genetic variation and phenotypic diversity, until now, no efficient commercial vaccines or therapeutic options are available. The ASFV genome contains a conserved middle region and two flexible ends that code for five multigene families (MGFs), while the biological functions of the MGFs are not fully characterized. Here, ASFV MGF505-2R-deficient mutant ASFV-Δ2R was constructed based on a highly virulent genotype II field isolate ASFV CN/GS/2018 currently circulating in China. Transcriptomic profiling demonstrated that ASFV-Δ2R was capable of inducing a larger number of differentially expressed genes (DEGs) compared with ASFV CN/GS/2018. Hierarchical clustering of up-regulated DEGs revealed that ASFV-Δ2R induced the most dramatic expression of interferon-related genes and inflammatory and innate immune genes, as further validated by RT-qPCR. The GO and KEGG pathway analysis identified significantly enriched pathways involved in pathogen recognition and innate antiviral immunity. Conversely, pharmacological activation of those antiviral immune responses by exogenous cytokines, including type I/II IFNs, TNF-α and IL-1ß, exerted combinatory effects and synergized in antiviral capacity against ASFV replication. Collectively, MGF505-2R is a newly identified inhibitor of innate immunity potentially implicated in immune evasion.
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Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana , Interferón Tipo I , Porcinos , Animales , Virus de la Fiebre Porcina Africana/genética , Fiebre Porcina Africana/prevención & control , Inmunidad Innata/genética , AntiviralesRESUMEN
Rotavirus (RV) is a non-enveloped icosahedral virus with an 11-segment double-stranded RNA genome, belonging to the family of rotaviruses. RV is one of the pathogens causing diarrhea in infants and young animals, and it induces the production of type I interferons (IFNs), which can trigger antiviral function by inducing the production of interferon-stimulated genes (ISGs). Although IFITM3, an ISG localizing to late endosomes, can limit many viral infections, whether or not it restricts the infection of RV is still unknown. Therefore, we attempted to determine whether IFITM3 also restricts RV infection by using over-expression and knockout cell strains. It was found that IFITM3-expressing cell strains were less susceptible to RV infection, as the replication of RV in over-expressing cells was significantly less than in control group cells. Correspondingly, IFITM3-knockout cells were significantly susceptible compared to the normal cells. Furthermore, the IFN-induced antiviral effect was significantly attenuated in the absence of IFITM3, and IFITM3 delayed RV escape from endosomes in the presence of IFITM3, suggesting that endogenous IFITM3 is of great importance in type I IFN-mediated antiviral responses and may restrict infection by affecting the function of the late endosomal compartment. In conclusion, these data provide the first evidence that IFITM3 limits RV infection in vitro and delays RV escape from late endosomes into the cytoplasm.
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Interferón Tipo I , Infecciones por Rotavirus , Rotavirus , Animales , Infecciones por Rotavirus/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Rotavirus/metabolismo , Antivirales , Replicación ViralRESUMEN
The pandemic due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has emerged as a serious global public health issue. Besides the high transmission rate from individual to individual, indirect transmission from inanimate objects or surfaces poses a more significant threat. Since the start of the outbreak, the importance of respiratory protection, social distancing, and chemical disinfection to prevent the spread of the virus has been the prime focus for infection control. Health regulatory organizations have produced guidelines for the formulation and application of chemical disinfectants to manufacturing industries and the public. On the other hand, extensive literature on the virucidal efficacy testing of microbicides for SARS-CoV-2 has been published over the past year and a half. This review summarizes the studies on the most common chemical disinfectants and their virucidal efficacy against SARS-CoV-2, including the type and concentration of the chemical disinfectant, the formulation, the presence of excipients, the exposure time, and other critical factors that determine the effectiveness of chemical disinfectants. In this review, we also critically appraise these disinfectants and conduct a discussion on the role they can play in the COVID-19 pandemic.
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COVID-19 , Desinfectantes , COVID-19/prevención & control , Desinfectantes/farmacología , Desinfección , Humanos , Pandemias/prevención & control , SARS-CoV-2RESUMEN
Modern human activity is profoundly changing our relationship with microorganisms with the startling rise in the rate of emerging infectious diseases. Nipah virus together with Ebola virus and SARS-CoV-2 are prominent examples. Since COVID-19 and the West African Ebola virus disease outbreak, different chemical disinfectants have been developed for preventing the direct spread of viruses and their efficacy has also been evaluated. However, there are currently no published efficacy studies for the chemical disinfection of Nipah virus. In this study, the virucidal efficacy of three disinfectants (Micro-Chem Plus detergent disinfectant cleaner, FWD and Medical EtOH) against Nipah virus was evaluated in quantitative suspension tests including. Our results showed that the > 4 log reduction achieved for all products in inactivating Nipah virus in 15 s. Even, 19% ethanol was able to inactivate Nipah virus when applied for at least 8 min contact time. Comparative analysis displayed virucidal efficacy of each of the evaluated disinfectants against SARS-CoV-2, Ebola virus and Nipah virus, with only minor differences in working concentrations and contact times required for complete inactivation. We expect that our study can assist in decontamination in healthcare settings and high level biosafety laboratories and can be beneficial to control for emerging enveloped viruses.
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COVID-19 , Desinfectantes , Ebolavirus , Virus Nipah , Desinfectantes/farmacología , Humanos , SARS-CoV-2RESUMEN
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), as the pathogen of coronavirus disease 2019 (COVID-19), has infected millions of people and took hundreds of thousands of lives. Unfortunately, there is deficiency of effective medicines to prevent or treat COVID-19. 3C like protease (3CLPro) of SARS-CoV-2 is essential to the viral replication and transcription, and is an attractive target to develop anti-SARS-CoV-2 agents. Targeting on the 3CLPro, we screened our protease inhibitor library and obtained compound 10a as hit to weakly inhibit the SARS-CoV-2 3CLPro, and determined the co-crystal structure of 10a and the protease. Based on the deep understanding on the protein-ligand complexes between the hit and SARS-CoV-2 3CLPro, we designed a series of peptidomimetic inhibitors, with outstanding inhibitory activity against SARS-CoV-2 3CLPro and excellent anti-viral potency against SARS-CoV-2. The protein-ligand complexes of the other key inhibitors with SARS-CoV-2 3CLPro were explicitly described by the X-ray co-crystal study. All such results suggest these peptidomimetic inhibitors could be further applied as encouraging drug candidates.
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Tratamiento Farmacológico de COVID-19 , Peptidomiméticos , Antivirales/química , Cisteína Endopeptidasas/química , Humanos , Ligandos , Péptido Hidrolasas , Peptidomiméticos/química , Peptidomiméticos/farmacología , Inhibidores de Proteasas/química , SARS-CoV-2RESUMEN
Inland waters (rivers, reservoirs, lakes, ponds, streams) and estuaries are significant emitters of methane (CH4 ) and nitrous oxide (N2 O) to the atmosphere, while global estimates of these emissions have been hampered due to the lack of a worldwide comprehensive data set of CH4 and N2 O flux components. Here, we synthesize 2997 in-situ flux or concentration measurements of CH4 and N2 O from 277 peer-reviewed publications to estimate global CH4 and N2 O emissions from inland waters and estuaries. Inland waters including rivers, reservoirs, lakes, and streams together release 95.18 Tg CH4 year-1 (ebullition plus diffusion) and 1.48 Tg N2 O year-1 (diffusion) to the atmosphere, yielding an overall CO2 -equivalent emission total of 3.06 Pg CO2 year-1 . The estimate of CH4 and N2 O emissions represents roughly 60% of CO2 emissions (5.13 Pg CO2 year-1 ) from these four inland aquatic systems, among which lakes act as the largest emitter for both CH4 and N2 O. Ebullition showed as a dominant flux component of CH4 , contributing up to 62%-84% of total CH4 fluxes across all inland waters. Chamber-derived CH4 emission rates are significantly greater than those determined by diffusion model-based methods for commonly capturing of both diffusive and ebullitive fluxes. Water dissolved oxygen (DO) showed as a dominant factor among all variables to influence both CH4 (diffusive and ebullitive) and N2 O fluxes from inland waters. Our study reveals a major oversight in regional and global CH4 budgets from inland waters, caused by neglecting the dominant role of ebullition pathways in those emissions. The estimated indirect N2 O EF5 values suggest that a downward refinement is required in current IPCC default EF5 values for inland waters and estuaries. Our findings further indicate that a comprehensive understanding of the magnitude and patterns of CH4 and N2 O emissions from inland waters and estuaries is essential in defining the way of how these aquatic systems will shape our climate.
Asunto(s)
Gases de Efecto Invernadero , Óxido Nitroso , Dióxido de Carbono/análisis , Estuarios , Gases de Efecto Invernadero/análisis , Metano/análisis , Óxido Nitroso/análisisRESUMEN
MicroRNAs (miRNAs) play an important role in the virus-host interaction. Our previous work has indicated that the expression level of miR-10a increased in porcine alveolar macrophages (PAMs) during porcine reproductive and respiratory syndrome virus (PRRSV) infection and further inhibited viral replication through downregulates the expression of host molecule signal-recognition particle 14 (SRP14) protein. However, the molecular mechanism of miR-10a increased after PRRSV infection remains unknown. In the present study, transcription factor interferon regulatory factor 8 (IRF8) was identified as a negative regulator of miR-10a. PRRSV infection decreases the expression level of IRF8 in PAMs, leading to upregulating miR-10a expression to play an anti-PRRSV role. Meanwhile, this work first proved that IRF8 promoted PRRSV replication in an miR-10a-dependent manner. Further, we explained that SRP14, the target gene of miR-10a, promotes the synthesis of the PRRSV genome by interacting with the viral components Nsp2, thus facilitating PRRSV replication. In conclusion, we identified a novel IRF8-miR-10a-SRP14 regulatory pathway against PRRSV infection, which provides new insights into virus-host interactions and suggests potential new antiviral strategies to control PRRSV. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) has rapidly spread to the global pig industry and caused incalculable economic damage since first discovered in the 1980s. However, conventional vaccines do not provide satisfactory protection. Understanding the molecular mechanisms of host resistance to PRRSV infection is necessary to develop safe and effective strategies to control PRRSV. During viral infection, miRNAs play vital roles in regulating the expression of viral or host genes at the posttranscriptional level. The significance of our study is that we revealed the transcriptional regulation mechanism of the antiviral molecule miR-10a after PRRSV infection. Moreover, our research also explained the mechanism of host molecule SRP14, the target gene of miR-10a regulating PRRSV replication. Thus, we report a novel regulatory pathway of IRF8-miR-10a-SRP14 against PRRSV infection, which provides new insights into virus-host interactions and suggests potential new control measures for future PRRSV outbreaks.
Asunto(s)
MicroARNs , Síndrome Respiratorio y de la Reproducción Porcina , Virus del Síndrome Respiratorio y Reproductivo Porcino , Animales , Antivirales/metabolismo , Línea Celular , Regulación de la Expresión Génica/inmunología , Interacciones Microbiota-Huesped/inmunología , Factores Reguladores del Interferón/genética , Factores Reguladores del Interferón/inmunología , Macrófagos Alveolares , MicroARNs/genética , MicroARNs/inmunología , Síndrome Respiratorio y de la Reproducción Porcina/inmunología , Síndrome Respiratorio y de la Reproducción Porcina/virología , Virus del Síndrome Respiratorio y Reproductivo Porcino/genética , Virus del Síndrome Respiratorio y Reproductivo Porcino/inmunología , Porcinos , Replicación Viral/genéticaRESUMEN
The diversity of porcine reproductive and respiratory syndrome virus (PRRSV) in China is increasing rapidly along with mutation and recombination. Recombination could occur between inter- and intra-lineage of PRRSV, which accelerated the complexity of pathogenicity and cell tropism of the recombinant strain. In the present study, a novel PRRSV strain named HN-YL1711 was isolated from a pig farm suffering from severe respiratory difficulty in Henan province, China. The whole genomic sequence analysis indicated that the genome of HN-YL1711 was 15018 nt. It shared 86%, 87.3%, 88.1%, 91.1%, 84.2%, and 84.1% nucleotide similarities with PRRSVs VR2332, CH1a, JXA1, NADC30, QYYZ, and GM2, respectively. Based on phylogenetic analysis of Nsp2, ORF5 and complete genomes, HN-YL1711 was classified into lineage 1 of PRRSV. However, seven genomic break points were detected in recombination analysis, which indicated that the HN-YL1711 originated from multiple recombination among NADC30-like (major parent, lineage 1), JXA1-like (minor parent, lineage 8), and QYYZ-like (minor parent, lineage 3) PRRSV. Porcine alveolar macrophages (PAMs), 3D4/21-CD163 and MARC-145 cells were used to explore the viral adaptation of HN-YL1711. The results indicated that it could infect the PAMs but failed to infect MARC-145 cells. Challenge experiments showed that HN-YL1711 exhibits intermediate virulence in pigs, compared with HP-PRRSV JXA1 and LP-PRRSV CH1a. Taken together, our findings suggest that recombination remains an important factor in PRRSV evolution and that recombination further complicates the cell tropism and pathogenicity of PRRSV.