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 an...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 SXYL1806.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.展开更多
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 commer...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-αand IL-1β,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.展开更多
The coronavirus disease 2019(COVID-19)pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which is spread primary via respiratory droplets and infects the lungs.Current...The coronavirus disease 2019(COVID-19)pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which is spread primary via respiratory droplets and infects the lungs.Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines(transformed or cancer cells)and species differences between animals and humans.Organoids are stem cell-derived selforganized three-dimensional culture in vitro and model the physiological conditions of natural organs.Here we showed that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells(hESCs)-derived lung organoids,including airway and alveolar organoids which covered the complete infection and spread route for SARS-CoV-2 within lungs.The infected ceils were ciliated,club,and alveolar type 2(AT2)cells,which were sequentially located from the proximal to the distal airway and terminal alveoli,respectively.Additionally,RNA-seq revealed early cell response to virus infection including an unexpected downregulation of the metabolic processes,especially lipid metabolism,in addition to the well-known upregulation of immune response.Further,Remdesivir and a human neutralizing antibody potently inhibited SARS-CoV-2 replication in lung organoids.Therefore,human lung organoids can serve as a pathophysiological model to investigate the underlying mechanism of SARS-CoV-2 infection and to discover and test therapeutic drugs for COVID-19.展开更多
Wastewater-based epidemiology(WBE)has emerged as an effective environmental surveillance tool in monitoring fecal-oral pathogen infections within a community.Congruently,SARS-Co V-2,the etiologic agent of COVID-19,has...Wastewater-based epidemiology(WBE)has emerged as an effective environmental surveillance tool in monitoring fecal-oral pathogen infections within a community.Congruently,SARS-Co V-2,the etiologic agent of COVID-19,has been demonstrated to infect the gastrointestinal tissues,and be shed in feces.In the present study,SARS-Co V-2 RNA was concentrated from wastewater,sludge,surface water,ground water,sediment,and soil samples of municipal and hospital wastewater systems and related environments in Wuhan during the COVID-19 middle and low risk periods,and the viral RNA copies quantified using reverse transcription quantitative polymerase chain reaction(RT-q PCR).From the findings of this study,during the middle risk period,one influent sample and three secondary effluents collected from waste water treatment plant 2,as well as two samples from Jinyintan Hospital wastewater system influent were SARS-Co V-2 RNA positive.One sludge sample collected from Guanggu Branch of Tongji Hospital,which was obtained during the low risk period,was also positive for SARS-Co V-2 RNA.These study findings demonstrate the significance of WBE in continuous surveillance of SARS-Co V-2 at the community level,even when the COVID-19 prevalence is low.Overall,this study can be used as an important reference for contingency management of wastewater treatment plants and COVID-19 prevention and control departments of Wuhan.展开更多
Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARSCoV-2), the etiologic agent of COVID-19, is an enveloped,positive-sense single-stranded RNA virus that first discovered in December 2019 from a seafood m...Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARSCoV-2), the etiologic agent of COVID-19, is an enveloped,positive-sense single-stranded RNA virus that first discovered in December 2019 from a seafood market in Wuhan, China(Zhou et al. 2020).展开更多
基金This research was supported by the National Natural Science Foundation of China(32172846)the Earmarked Fund for CARS-35,the Science and Technology Major Project of Gansu Province(22ZD6NA001)+4 种基金the Science Foundation for Distinguished Young Scholars of Shaanxi Province(2021JC-18)the Natural Science Foundation of Gansu Province(23JRRA1153)the Science and Technology Plan Project of Gansu Province(23JRRA561)the Chinese Academy of Agricultural Science and Technology Innovation Project(CAAS-ASTIP-JBGS-20210602)the Strategic Priority Research Program of the National Center of Technology Innovation for Pigs(NCTIP-XD/C03).
文摘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 SXYL1806.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.
基金supported by grants from the National Key R&D Program of China(2021YFD1801300)the Key-Area Research and Development Program of Guangdong Province(grant number 2019B020211003)+2 种基金the Chinese Academy of Agricultural Science and Technology Innovation Project(grants number CAAS-ZDRW202006 and CAAS-ASTIP-2021-LVRI)Technology Major Projects of Gansu Province(20ZD7A006 and NCC0006)as well as funding from the director of Lanzhou Veterinary Research Institute(LVRI-SZJJ-202106).
文摘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-αand IL-1β,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.
基金This work was supported by grants from National Natural Science Foundation of China(Grant Nos.82070002,82072329,81872511,and 81670093)Frontier Research Program of Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory)(2018GZR110105005)+6 种基金National Science and Technology Major Project(2018ZX10301101)the Natural Science Foundation of Guangdong Province(2018A030313455)the Program of Department of Science and Technology of Guangdong Province(2014B020212018)National Key Research and Development Project(2018YFA0507201)the special project for COVID-19 of Guangzhou Regenerative Medicine and Health Guangdong Labo・ratory(2020GZR110106006)the emergency grants for prevention and control of SARS-CoV-2 of Guangdong province(2020B111108001)National Postdoctoral Program for Innovative Talent(BX20190089).
文摘The coronavirus disease 2019(COVID-19)pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which is spread primary via respiratory droplets and infects the lungs.Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines(transformed or cancer cells)and species differences between animals and humans.Organoids are stem cell-derived selforganized three-dimensional culture in vitro and model the physiological conditions of natural organs.Here we showed that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells(hESCs)-derived lung organoids,including airway and alveolar organoids which covered the complete infection and spread route for SARS-CoV-2 within lungs.The infected ceils were ciliated,club,and alveolar type 2(AT2)cells,which were sequentially located from the proximal to the distal airway and terminal alveoli,respectively.Additionally,RNA-seq revealed early cell response to virus infection including an unexpected downregulation of the metabolic processes,especially lipid metabolism,in addition to the well-known upregulation of immune response.Further,Remdesivir and a human neutralizing antibody potently inhibited SARS-CoV-2 replication in lung organoids.Therefore,human lung organoids can serve as a pathophysiological model to investigate the underlying mechanism of SARS-CoV-2 infection and to discover and test therapeutic drugs for COVID-19.
基金supported by the Wuhan Bureau of Science and Technology(No.202002020101010022)China Geological Survey(No.DD20190282)the support team from the National Biosafety Laboratory in Wuhan,China,for the support they extended to us。
文摘Wastewater-based epidemiology(WBE)has emerged as an effective environmental surveillance tool in monitoring fecal-oral pathogen infections within a community.Congruently,SARS-Co V-2,the etiologic agent of COVID-19,has been demonstrated to infect the gastrointestinal tissues,and be shed in feces.In the present study,SARS-Co V-2 RNA was concentrated from wastewater,sludge,surface water,ground water,sediment,and soil samples of municipal and hospital wastewater systems and related environments in Wuhan during the COVID-19 middle and low risk periods,and the viral RNA copies quantified using reverse transcription quantitative polymerase chain reaction(RT-q PCR).From the findings of this study,during the middle risk period,one influent sample and three secondary effluents collected from waste water treatment plant 2,as well as two samples from Jinyintan Hospital wastewater system influent were SARS-Co V-2 RNA positive.One sludge sample collected from Guanggu Branch of Tongji Hospital,which was obtained during the low risk period,was also positive for SARS-Co V-2 RNA.These study findings demonstrate the significance of WBE in continuous surveillance of SARS-Co V-2 at the community level,even when the COVID-19 prevalence is low.Overall,this study can be used as an important reference for contingency management of wastewater treatment plants and COVID-19 prevention and control departments of Wuhan.
基金supported by the Ministry of Science and Technology of the People’s Republic of China (2020YFC08845600)the National Health Commission of the People’s Republic of China (2018ZX10711001-006)。
文摘Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARSCoV-2), the etiologic agent of COVID-19, is an enveloped,positive-sense single-stranded RNA virus that first discovered in December 2019 from a seafood market in Wuhan, China(Zhou et al. 2020).