Objective:Through interviews with oral specialist nurses,to explore the influencing factors of training transfer for oral specialist nurses,and provide references for scientifically improving the effect of specialist ...Objective:Through interviews with oral specialist nurses,to explore the influencing factors of training transfer for oral specialist nurses,and provide references for scientifically improving the effect of specialist nurse training transfer.Methods:Using purposive sampling and descriptive qualitative research,15 oral specialist nurses from two tertiary hospitals in Guangdong Province were selected for semi-structured interviews,and data analysis was performed.Results:After collating and analyzing the interview data,three types of factors affecting the training transfer of oral specialist nurses were proposed,including personal characteristics,training management,and training transfer atmosphere.Conclusion:Managers should formulate a comprehensive and systematic plan based on the influencing factors of oral specialist nurse training transfer to effectively promote training transfer behavior and enhance training transfer effects.展开更多
The global dissemination of H5 avian influenza viruses represents a significant threat to both human and animal health.In thisstudy,we conducted a genome-wide siRNA library screening against the highly pathogenic H5N1 i...The global dissemination of H5 avian influenza viruses represents a significant threat to both human and animal health.In thisstudy,we conducted a genome-wide siRNA library screening against the highly pathogenic H5N1 influenza virus,leading us tothe identification of 457 cellular cofactors(441 proviral factors and 16 antiviral factors)involved in the virus replication cycle.Gene Ontology term enrichment analysis revealed that the candidate gene data sets were enriched in gene categoriesassociated with mRNA splicing via spliceosome in the biological process,integral component of membrane in the cellularcomponent,and protein binding in the molecular function.Reactome pathway analysis showed that the immune system(up to63 genes)was the highest enriched pathway.Subsequent comparisons with four previous siRNA library screenings revealedthat the overlapping rates of the involved pathways were 8.53%-62.61%,which were significantly higher than those of thecommon genes(1.85%-6.24%).Together,our genome-wide siRNA library screening unveiled a panorama of host cellularnetworks engaged in the regulation of highly pathogenic H5N1 influenza virus replication,which may provide potential targetsand strategies for developing novel antiviral countermeasures.展开更多
Influenza A virus(IAV) commandeers numerous host cellular factors for successful replication. However, very few host factors have been revealed to be involved in the fusion of viral envelope and late endosomal membran...Influenza A virus(IAV) commandeers numerous host cellular factors for successful replication. However, very few host factors have been revealed to be involved in the fusion of viral envelope and late endosomal membranes. In this study, we identified cation-dependent mannose-6-phosphate receptor(M6PR) as a crucial host factor for the replication of IAV. We found that siRNA knockdown of M6PR expression significantly reduced the growth titers of different subtypes of IAV, and that the inhibitory effect of M6PR siRNA treatment on IAV growth was overcome by the complement of exogenously expressed M6PR. When A549 cells were treated with siRNA targeting M6PR,the nuclear accumulation of viral nucleoprotein(NP) was dramatically inhibited at early timepoints post-infection, indicating that M6PR engages in the early stage of the IAV replication cycle. By investigating the role of M6PR in the individual entry and post-entry steps of IAV replication, we found that the downregulation of M6PR expression had no effect on attachment, internalization, early endosome trafficking,or late endosome acidification. However, we found that M6PR expression was critical for the fusion of viral envelope and late endosomal membranes. Of note, M6PR interacted with the hemagglutinin(HA) protein of IAV, and further studies showed that the lumenal domain of M6PR and the ectodomain of HA2 mediated the interaction and directly promoted the fusion of the viral and late endosomal membranes,thereby facilitating IAV replication. Together, our findings highlight the importance of the M6PR–HA interaction in the fusion of viral and late endosomal membranes during IAV replication.展开更多
The H5N8 avian influenza viruses have been widely circulating in wild birds and are responsible for the loss of over 33 million domestic poultry in Europe, Russia, Middle East, and Asia since January 2020. To monitor ...The H5N8 avian influenza viruses have been widely circulating in wild birds and are responsible for the loss of over 33 million domestic poultry in Europe, Russia, Middle East, and Asia since January 2020. To monitor the invasion and spread of the H5N8 virus in China, we performed active surveillance by analyzing 317 wild bird samples and swab samples collected from 41,172 poultry all over the country. We isolated 22 H5N8 viruses from wild birds and 14 H5N8 viruses from waterfowls. Genetic analysis indicated that the 36 viruses formed two different genotypes: one genotype viruses were widely detected from different wild birds and domestic waterfowls;the other genotype was isolated from a whopper swan. We further revealed the origin and spatiotemporal spread of these two distinct H5N8 virus genotypes in 2020 and 2021. Animal studies indicated that the H5N8 isolates are highly pathogenic to chickens, mildly pathogenic in ducks, but have distinct pathotypes in mice. Moreover, we found that vaccinated poultry in China could be completely protected against H5N8 virus challenge. Given that the H5N8 viruses are likely to continue to spread in wild birds, vaccination of poultry is highly recommended in high-risk countries to prevent H5N8 avian influenza.展开更多
Tripartite motif(TRIM)family proteins are important effectors of innate immunity against viral infections.Here we identified TRIM35 as a regulator of TRAF3 activation.Deficiency in or inhibition of TRIM35 suppressed t...Tripartite motif(TRIM)family proteins are important effectors of innate immunity against viral infections.Here we identified TRIM35 as a regulator of TRAF3 activation.Deficiency in or inhibition of TRIM35 suppressed the production of type I interferon(IFN)in response to viral infection.777m35-deficient mice were more susceptible to influenza A virus(IAV)infection than were wild-type mice.TRIM35 promoted the RIG-Imediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and TBK1.IAV PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of TRAF3.TRIM35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2,thereby antagonizing its suppression of TRAF3 activation.Our in vitro and in vivo findings thus reveal novel roles of TRIM35,through catalyzing Lys63-or Lys48-linked polyubiquitination,in RIG-I antiviral immunity and mechanism of defense against IAV infection.展开更多
As a major component of the viral ribonucleoprotein(vRNP)complex in influenza A virus(IAV),nucleoprotein(NP)interacts with isoforms of importinαfamily members,leading to the import of itself and vRNP complex into the...As a major component of the viral ribonucleoprotein(vRNP)complex in influenza A virus(IAV),nucleoprotein(NP)interacts with isoforms of importinαfamily members,leading to the import of itself and vRNP complex into the nucleus,a process pivotal in the replication cycle of IAV.In this study,we found that BinCARD1,an isoform of Bcl10-interacting protein with CARD(BinCARD),was leveraged by IAV for efficient viral replication.BinCARD1 promoted the nuclear import of the vRNP complex and newly synthesized NP and thus enhanced vRNP complex activity.Moreover,we found that BinCARD1 interacted with NP to promote NP binding to importinα7,an adaptor in the host nuclear import pathway.However,we also found that BinCARD1 promoted RIG-I-mediated innate immune signaling by mediating Lys63-linked polyubiquitination of TRAF3,and that TBK1 appeared to degrade BinCARD1.We showed that BinCARD1 was polyubiquitinated at residue K103 through a Lys63 linkage,which was recognized by the TBK1-p62 axis for autophagic degradation.Overall,our data demonstrate that IAV leverages BinCARD1 as an important host factor that promotes viral replication,and two mechanisms in the host defense system are triggered—innate immune signaling and autophagic degradation—to mitigate the promoting effect of BinCARD1 on the life cycle of IAV.展开更多
Animal influenza viruses continue to pose a threat to human public health. The Eurasian avian-like H1N1(EA H1N1) viruses are widespread in pigs throughout Europe and China and have caused human infections in several c...Animal influenza viruses continue to pose a threat to human public health. The Eurasian avian-like H1N1(EA H1N1) viruses are widespread in pigs throughout Europe and China and have caused human infections in several countries, indicating their pandemic potential. To carefully monitor the evolution of the EA H1N1 viruses in nature, we collected nasal swabs from 103,110pigs in 22 provinces in China between October 2013 and December 2019, and isolated 855 EA H1N1 viruses. Genomic analysis of 319 representative viruses revealed that these EA H1N1 viruses formed eight different genotypes through reassortment with viruses of other lineages circulating in humans and pigs, and two of these genotypes(G4 and G5) were widely distributed in pigs.Animal studies indicated that some strains have become highly pathogenic in mice and highly transmissible in ferrets via respiratory droplets. Moreover, two-thirds of the EA H1N1 viruses reacted poorly with ferret serum antibodies induced by the currently used H1N1 human influenza vaccine, suggesting that existing immunity may not prevent the transmission of the EA H1N1 viruses in humans. Our study reveals the evolution and pandemic potential of EA H1N1 viruses and provides important insights for future pandemic preparedness.展开更多
Dear Editor,In the last century,H1N1,H2N2,and H3N2 influenza viruses caused pandemics in 1918,1957,and 1968,respectively.In 2009,a novel H1N1 reassortant jumped from pigs to humans and caused a fourth influenza pandem...Dear Editor,In the last century,H1N1,H2N2,and H3N2 influenza viruses caused pandemics in 1918,1957,and 1968,respectively.In 2009,a novel H1N1 reassortant jumped from pigs to humans and caused a fourth influenza pandemic.Different lineages of H3N2 influenza viruses are commonly found in animal reservoirs.If a different lineage of H3N2 virus jumps to humans,another human influenza pandemic could occur with devastating consequences.展开更多
Antigenic drift forces us to frequently update influenza vaccines; however, the genetic basis for antigenic variation remains largely unknown. In this study, we used clade 7.2 H5 viruses as models to explore the molec...Antigenic drift forces us to frequently update influenza vaccines; however, the genetic basis for antigenic variation remains largely unknown. In this study, we used clade 7.2 H5 viruses as models to explore the molecular determinants of influenza virus antigenic variation. We generated eight monoclonal antibodies(MAbs) targeted to the hemagglutinin(HA) protein of the index virus A/chicken/Shanxi/2/2006 and found that two representative antigenically drifted clade 7.2 viruses did not react with six of the eight MAbs. The E131 N mutation and insertion of leucine at position 134 in the HA protein of the antigenically drifted strains eliminated the reactivity of the virus with the MAbs. We also found that the amino acid N131 in the H5 HA protein is glycosylated. Our results provide experimental evidence that glycosylation and an amino acid insertion or deletion in HA influence antigenic variation.展开更多
文摘Objective:Through interviews with oral specialist nurses,to explore the influencing factors of training transfer for oral specialist nurses,and provide references for scientifically improving the effect of specialist nurse training transfer.Methods:Using purposive sampling and descriptive qualitative research,15 oral specialist nurses from two tertiary hospitals in Guangdong Province were selected for semi-structured interviews,and data analysis was performed.Results:After collating and analyzing the interview data,three types of factors affecting the training transfer of oral specialist nurses were proposed,including personal characteristics,training management,and training transfer atmosphere.Conclusion:Managers should formulate a comprehensive and systematic plan based on the influencing factors of oral specialist nurse training transfer to effectively promote training transfer behavior and enhance training transfer effects.
基金supported by the National Key Research and DevelopmentProgram of China(2021YFD1800203 and 2021YFD1800204)the National Natural Science Foundation of China(NSFC)(32192453,32272979,and 32172847)+2 种基金the China PostdoctoralScience Foundation(2019M660897)the Innovation Program ofChinese Academy of Agricultural Sciences(CAAS-CSLPDCP-202401)the Earmarked Fund for China Agriculture Re-search System(CARS-41-G12)。
文摘The global dissemination of H5 avian influenza viruses represents a significant threat to both human and animal health.In thisstudy,we conducted a genome-wide siRNA library screening against the highly pathogenic H5N1 influenza virus,leading us tothe identification of 457 cellular cofactors(441 proviral factors and 16 antiviral factors)involved in the virus replication cycle.Gene Ontology term enrichment analysis revealed that the candidate gene data sets were enriched in gene categoriesassociated with mRNA splicing via spliceosome in the biological process,integral component of membrane in the cellularcomponent,and protein binding in the molecular function.Reactome pathway analysis showed that the immune system(up to63 genes)was the highest enriched pathway.Subsequent comparisons with four previous siRNA library screenings revealedthat the overlapping rates of the involved pathways were 8.53%-62.61%,which were significantly higher than those of thecommon genes(1.85%-6.24%).Together,our genome-wide siRNA library screening unveiled a panorama of host cellularnetworks engaged in the regulation of highly pathogenic H5N1 influenza virus replication,which may provide potential targetsand strategies for developing novel antiviral countermeasures.
基金supported by the National Natural Science Foundation of China(32192453,32172847)the National Key Research and Development Program of China(2021YFD1800204)+1 种基金the Laboratory of Lingnan Modern Agriculture Project(NT2021007)the earmarked fund for CARS-41。
文摘Influenza A virus(IAV) commandeers numerous host cellular factors for successful replication. However, very few host factors have been revealed to be involved in the fusion of viral envelope and late endosomal membranes. In this study, we identified cation-dependent mannose-6-phosphate receptor(M6PR) as a crucial host factor for the replication of IAV. We found that siRNA knockdown of M6PR expression significantly reduced the growth titers of different subtypes of IAV, and that the inhibitory effect of M6PR siRNA treatment on IAV growth was overcome by the complement of exogenously expressed M6PR. When A549 cells were treated with siRNA targeting M6PR,the nuclear accumulation of viral nucleoprotein(NP) was dramatically inhibited at early timepoints post-infection, indicating that M6PR engages in the early stage of the IAV replication cycle. By investigating the role of M6PR in the individual entry and post-entry steps of IAV replication, we found that the downregulation of M6PR expression had no effect on attachment, internalization, early endosome trafficking,or late endosome acidification. However, we found that M6PR expression was critical for the fusion of viral envelope and late endosomal membranes. Of note, M6PR interacted with the hemagglutinin(HA) protein of IAV, and further studies showed that the lumenal domain of M6PR and the ectodomain of HA2 mediated the interaction and directly promoted the fusion of the viral and late endosomal membranes,thereby facilitating IAV replication. Together, our findings highlight the importance of the M6PR–HA interaction in the fusion of viral and late endosomal membranes during IAV replication.
基金supported by the National Natural Science Foundation of China (31521005, 31672593)the Laboratory for Lingnan Modern Agriculture Project (NT2021007)+1 种基金the National Key Research and Development Program of China (2016YFD0500201)the China Agriculture Research System (CARS-41G12)
文摘The H5N8 avian influenza viruses have been widely circulating in wild birds and are responsible for the loss of over 33 million domestic poultry in Europe, Russia, Middle East, and Asia since January 2020. To monitor the invasion and spread of the H5N8 virus in China, we performed active surveillance by analyzing 317 wild bird samples and swab samples collected from 41,172 poultry all over the country. We isolated 22 H5N8 viruses from wild birds and 14 H5N8 viruses from waterfowls. Genetic analysis indicated that the 36 viruses formed two different genotypes: one genotype viruses were widely detected from different wild birds and domestic waterfowls;the other genotype was isolated from a whopper swan. We further revealed the origin and spatiotemporal spread of these two distinct H5N8 virus genotypes in 2020 and 2021. Animal studies indicated that the H5N8 isolates are highly pathogenic to chickens, mildly pathogenic in ducks, but have distinct pathotypes in mice. Moreover, we found that vaccinated poultry in China could be completely protected against H5N8 virus challenge. Given that the H5N8 viruses are likely to continue to spread in wild birds, vaccination of poultry is highly recommended in high-risk countries to prevent H5N8 avian influenza.
基金The work was supported by the National Key Research and Development Program of China(2016YFD0500205)the National Natural Science Foundation of China(NSFC)(Grant Nos.31521005,31672582,31422054,and 31472215)+1 种基金the Natural Science Foundation of Heilongjiang Province(JQ2019C005)by the Central Public-Interest Scientific Institution Basal Research Fund(No.Y2017JC35).
文摘Tripartite motif(TRIM)family proteins are important effectors of innate immunity against viral infections.Here we identified TRIM35 as a regulator of TRAF3 activation.Deficiency in or inhibition of TRIM35 suppressed the production of type I interferon(IFN)in response to viral infection.777m35-deficient mice were more susceptible to influenza A virus(IAV)infection than were wild-type mice.TRIM35 promoted the RIG-Imediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and TBK1.IAV PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of TRAF3.TRIM35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2,thereby antagonizing its suppression of TRAF3 activation.Our in vitro and in vivo findings thus reveal novel roles of TRIM35,through catalyzing Lys63-or Lys48-linked polyubiquitination,in RIG-I antiviral immunity and mechanism of defense against IAV infection.
基金This investigation was funded by a grant from the Laboratory of Lingnan Modern Agriculture Project(NT2021007 to HC and CL)the National Natural Science Foundation of China(NSFC)(32192453 to CL,32172847 to LJ)+2 种基金the National Key Research and Development Program of China(2021YFD1800203 to HC,2021YFD1800204 to CL)the Natural Science Foundation of Heilongjiang Province(JQ2019C005 to CL)the Central Public-Interest Scientific Institution Basal Research Fund(Y2017JC35 to GT).
文摘As a major component of the viral ribonucleoprotein(vRNP)complex in influenza A virus(IAV),nucleoprotein(NP)interacts with isoforms of importinαfamily members,leading to the import of itself and vRNP complex into the nucleus,a process pivotal in the replication cycle of IAV.In this study,we found that BinCARD1,an isoform of Bcl10-interacting protein with CARD(BinCARD),was leveraged by IAV for efficient viral replication.BinCARD1 promoted the nuclear import of the vRNP complex and newly synthesized NP and thus enhanced vRNP complex activity.Moreover,we found that BinCARD1 interacted with NP to promote NP binding to importinα7,an adaptor in the host nuclear import pathway.However,we also found that BinCARD1 promoted RIG-I-mediated innate immune signaling by mediating Lys63-linked polyubiquitination of TRAF3,and that TBK1 appeared to degrade BinCARD1.We showed that BinCARD1 was polyubiquitinated at residue K103 through a Lys63 linkage,which was recognized by the TBK1-p62 axis for autophagic degradation.Overall,our data demonstrate that IAV leverages BinCARD1 as an important host factor that promotes viral replication,and two mechanisms in the host defense system are triggered—innate immune signaling and autophagic degradation—to mitigate the promoting effect of BinCARD1 on the life cycle of IAV.
基金supported by the National Key Research and Development Program of China(2021YFD1800200,2021YFC2301700)。
文摘Animal influenza viruses continue to pose a threat to human public health. The Eurasian avian-like H1N1(EA H1N1) viruses are widespread in pigs throughout Europe and China and have caused human infections in several countries, indicating their pandemic potential. To carefully monitor the evolution of the EA H1N1 viruses in nature, we collected nasal swabs from 103,110pigs in 22 provinces in China between October 2013 and December 2019, and isolated 855 EA H1N1 viruses. Genomic analysis of 319 representative viruses revealed that these EA H1N1 viruses formed eight different genotypes through reassortment with viruses of other lineages circulating in humans and pigs, and two of these genotypes(G4 and G5) were widely distributed in pigs.Animal studies indicated that some strains have become highly pathogenic in mice and highly transmissible in ferrets via respiratory droplets. Moreover, two-thirds of the EA H1N1 viruses reacted poorly with ferret serum antibodies induced by the currently used H1N1 human influenza vaccine, suggesting that existing immunity may not prevent the transmission of the EA H1N1 viruses in humans. Our study reveals the evolution and pandemic potential of EA H1N1 viruses and provides important insights for future pandemic preparedness.
基金This work was supported by the National Key Research and Development Program of China(2016YFD0500201,2016YFD0500203)the National Natural Science Foundation of China(31521005)+1 种基金the China Agriculture Research System(CARS-41-G12)the Central Public-interest Scientific Institution Basal Research Fund(1610302017001).
文摘Dear Editor,In the last century,H1N1,H2N2,and H3N2 influenza viruses caused pandemics in 1918,1957,and 1968,respectively.In 2009,a novel H1N1 reassortant jumped from pigs to humans and caused a fourth influenza pandemic.Different lineages of H3N2 influenza viruses are commonly found in animal reservoirs.If a different lineage of H3N2 virus jumps to humans,another human influenza pandemic could occur with devastating consequences.
基金supported by the National Natural Science Foundation of China (31521005, 31672593)the National Key R&D Program of China (2016YFD0500201, 2016YFD0500203)the China Agriculture Research System (CARS-41-G12)
文摘Antigenic drift forces us to frequently update influenza vaccines; however, the genetic basis for antigenic variation remains largely unknown. In this study, we used clade 7.2 H5 viruses as models to explore the molecular determinants of influenza virus antigenic variation. We generated eight monoclonal antibodies(MAbs) targeted to the hemagglutinin(HA) protein of the index virus A/chicken/Shanxi/2/2006 and found that two representative antigenically drifted clade 7.2 viruses did not react with six of the eight MAbs. The E131 N mutation and insertion of leucine at position 134 in the HA protein of the antigenically drifted strains eliminated the reactivity of the virus with the MAbs. We also found that the amino acid N131 in the H5 HA protein is glycosylated. Our results provide experimental evidence that glycosylation and an amino acid insertion or deletion in HA influence antigenic variation.
