Due to the insufficient supply of embryonated chicken eggs,the preparation of large quantities of inactivated influenza vaccines will require an alternative virus culture system after the emergence or reemergence of a...Due to the insufficient supply of embryonated chicken eggs,the preparation of large quantities of inactivated influenza vaccines will require an alternative virus culture system after the emergence or reemergence of a pandemic influenza virus.The Vero cell is one of the ideal options since it was used for producing many kinds of human vaccines.However,most of the influenza viruses can not grow well in Vero cells.To develop a new influenza vaccine with Vero cells as a substrate,the virus needs to adapt to this cell substrate to maintain high growth characteristics.By serial passages in Vero cells,the B/Yunnan/2/2005va(B)strain was successfully adapted to Vero cells,with the hemagglutination titer(HAT)of the virus reaching 1:512.The high growth characteristic of this strain is stable up to 21 passages.The strain was identified by hemagglutination inhibition (HAI)test and sequencing respectively;the HA1 gene sequence of the virus was cloned and analyzed.The screening and establishment of high growth B virus provides an important tool for influenza vaccine production in Vero cells.展开更多
BACKGROUND Among the various types and causes of mesenteric ischemia,superior mesenteric vein(SMV)thrombosis is a rare and ambiguous disease.If a patient presents with SMV thrombosis,past medical history should be rev...BACKGROUND Among the various types and causes of mesenteric ischemia,superior mesenteric vein(SMV)thrombosis is a rare and ambiguous disease.If a patient presents with SMV thrombosis,past medical history should be reviewed,and the patient should be screened for underlying disease.SMV thrombosis may also occur due to systemic infection.In this report,we describe a case of SMV thrombosis complicated by influenza B infection.CASE SUMMARY A 64-year-old male visited the hospital with general weakness,muscle aches,fever,and abdominal pain.The patient underwent computed tomography(CT)and was diagnosed with SMV thrombosis.Since the patient’s muscle pain and fever could not be explained by the SMV thrombosis,the clinician performed a test for influenza,which produced a positive result for influenza B.The patient had a thrombus in the SMV only,with no invasion of the portal or splenic veins,and was clinically stable.Anticoagulation treatment was prescribed without surgery or other procedures.The follow-up CT scan showed improvement,and the patient was subsequently discharged with continued oral anticoagulant treatment.CONCLUSION This case provides evidence that influenza may be a possible risk factor for SMV thrombosis.If unexplained abdominal pain is accompanied by an influenza infection,examination of an abdominal CT scan may be necessary to screen for possible SMV thrombosis.展开更多
Neuromedin B(NMB)is a member of mammalian bombesin-like peptide family and almost all its potent biological actions take place exclusively through its receptor NMBR,which has been identified as a G-protein couple rece...Neuromedin B(NMB)is a member of mammalian bombesin-like peptide family and almost all its potent biological actions take place exclusively through its receptor NMBR,which has been identified as a G-protein couple receptor with seven trans-membrane regions.NMB and NMBR represent an interesting signaling axis over which NMB/NMBR perform multiple biological activities,in particularly,they have been highlighted in the regulation of the immunology system.This review aims to provide a brief overview of the recent advancements in our understanding regarding the potential immunological functions of NMB and NMBR in cell proliferation,tumorigenesis,angiogenesis,neurogenic inflammation,anti-influenza A virus(IAV)infections,and briefly discusses the potential importance of these observations.All these implicated that targeting NMBR or developing analogues of NMB may represent a useful strategy for development of new anti-IAV agents.展开更多
Taurolidine(TRD),a derivative of taurine,has anti-bacterial and anti-tumor effects by chemically reacting with cell-walls,endotoxins and exotoxins to inhibit the adhesion of microorganisms.However,its application in a...Taurolidine(TRD),a derivative of taurine,has anti-bacterial and anti-tumor effects by chemically reacting with cell-walls,endotoxins and exotoxins to inhibit the adhesion of microorganisms.However,its application in antiviral therapy is seldom reported.Here,we reported that TRD significantly inhibited the replication of influenza virus H5N1 in MDCK cells with the half-maximal inhibitory concentration(EC_(50))of 34.45μg/mL.Furthermore,the drug inhibited the amplification of the cytokine storm effect and improved the survival rate of mice lethal challenged with H5N1(protection rate was 86%).Moreover,TRD attenuated virus-induced lung damage and reduced virus titers in mice lungs.Administration of TRD reduced the number of neutrophils and increased the number of lymphocytes in the blood of H5N1 virus-infected mice.Importantly,the drug regulated the NF-κB signaling pathway by inhibiting the separation of NF-κB and IκBa,thereby reducing the expression of inflammatory factors.In conclusion,our findings suggested that TRD could act as a potential anti-influenza drug candidate in further clinical studies.展开更多
Annual influenza B virus epidemics and outbreaks cause severe influenza diseases in humans and pose a threat to public health. China is an important epidemic area of influenza B viruses. However, the spatial, temporal...Annual influenza B virus epidemics and outbreaks cause severe influenza diseases in humans and pose a threat to public health. China is an important epidemic area of influenza B viruses. However, the spatial, temporal transmission pathways and the demography history of influenza B viruses in China remain unknown. We collected the haemagglutinin gene sequences sampled of influenza B virus in China between 1973 and 2018. A Bayesian Markov chain Monte Carlo phylogeographic discrete approach was used to infer the spatial and temporal phylodynamics of influenza B virus. The Bayesian phylogeographic analysis of influenza B viruses showed that the North subtropical and South subtropical zones are the origins of the Victoria and Yamagata lineage viruses, respectively. Furthermore, the South temperate and North subtropical zones acted as transition nodes in the Victoria lineage virus dispersion network and that the North subtropical and Mid subtropical zones acted as transition nodes in the Yamagata lineage virus dispersion network. Our findings contribute to the knowledge regarding the spatial and temporal patterns of influenza B virus outbreaks in China.展开更多
Background: During the coronavirus disease 2019(COVID-19)pandemic,seasonal influenza activity declined globally and remained below previous seasonal levels,but intensified in China since 2021.Preventive measures to CO...Background: During the coronavirus disease 2019(COVID-19)pandemic,seasonal influenza activity declined globally and remained below previous seasonal levels,but intensified in China since 2021.Preventive measures to COVID-19 accompanied by different epidemic characteristics of influenza in different regions of the world.To better respond to influenza outbreaks under the COVID-19 pandemic,we analyzed the epidemiology,antigenic and genetic characteristics,and antiviral susceptibility of influenza viruses in the mainland of China during 2020–2021.Methods: Respiratory specimens from influenza like illness cases were collected by sentinel hospitals and sent to network laboratories in Chinese National Influenza Surveillance Network.Antigenic mutation analysis of influenza virus isolates was performed by hemagglutination inhibition assay.Next-generation sequencing was used for genetic analyses.We also conducted molecular characterization and phylogenetic analysis of circulating influenza viruses.Viruses were tested for resistance to antiviral medications using phenotypic and/or sequence-based methods.Results: In the mainland of China,influenza activity recovered in 2021 compared with that in 2020 and intensified during the traditional influenza winter season,but it did not exceed the peak in previous years.Almost all viruses isolated during the study period were of the B/Victoria lineage and were characterized by genetic diversity,with the subgroup 1A.3a.2 viruses currently predominated.37.8%viruses tested were antigenically similar to reference viruses representing the components of the vaccine for the 2020–2021 and 2021–2022 Northern Hemisphere influenza seasons.In addition,China has a unique subgroup of 1A.3a.1 viruses.All viruses tested were sensitive to neuraminidase inhibitors and endonuclease inhibitors,except two B/Victoria lineage viruses identified to have reduced sensitivity to neuraminidase inhibitors.Conclusions: Influenza activity increased in the mainland of China in 2021,and caused flu season in the winter of 2021–2022.Although the diversity of influenza(sub)type decreases,B/Victoria lineage viruses show increased genetic and antigenic diversity.The world needs to be fully prepared for the co-epidemic of influenza and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus globally.展开更多
As a leading cause of respiratory disease, influenza A virus(IAV) presents a pandemic threat in annual seasonal outbreaks. Given the limitation of existing anti-influenza therapies, there remains to be a requirement f...As a leading cause of respiratory disease, influenza A virus(IAV) presents a pandemic threat in annual seasonal outbreaks. Given the limitation of existing anti-influenza therapies, there remains to be a requirement for new drugs. Compound Yi-Zhi-Hao pellet(CYZH) is a famous traditional Chinese medicine(TCM) used in the clinic, whose formula has been recorded in Complication of National Standard for Traditional Chinese Medicine to treat common cold. In this study, we found that CYZH exhibited a broad-spectrum anti-influenza activity and inhibited the expression of viral RNA and proteins in vitro. Mechanistically, CYZH had no inhibitory activities against viral protein hemagglutinin and IAV RNA-dependent RNA polymerase. Instead, it induced activation of erythroid 2-related factor 2(Nrf2) and nuclear factor kappa B(NF-κB), which subsequently upregulated heme oxygenase-1(HO-1) expression.Also, CYZH protected cells from oxidative damage induced by reactive oxygen series. In conclusions,CYZH inhibits IAV replication in vitro, at least partly by activating expression of the Nrf2/HO-1 pathway.展开更多
Influenza virus (IAV)infection is a major cause of severe respiratory illness that affects almost every country in the world.IAV infections result in respiratory illness and even acute lung injury and death,but the un...Influenza virus (IAV)infection is a major cause of severe respiratory illness that affects almost every country in the world.IAV infections result in respiratory illness and even acute lung injury and death,but the underlying mechanisms responsible for IAV pathogenesis have not yet been fully elucidated.In this study,the basic fibroblast growth factor 2 (FGF2)level was markedly increased in H1N1 virus-infected humans and mice.FGF2,which is predominately derived from epithelial cells,recruits and activates neutrophils via the FGFR2-PI3K-AKT-NFKB signaling pathway.FGF2 depletion or knockout exacerbated influenzaassociated disease by impairing neutrophil recruitment and activation.More importantly,administration of the recombinant FGF2 protein significantly aUeviated the severity of IAV-induced lung injury and promoted the survival of IAV-infected mice.Based on the results from experiments in which neutrophils were depleted and adoptively transferred,FGF2 protected mice against IAV , infection by recruiting neutrophils.Thus,FGF2 plays a critical role in preventing IAV-induced lung injury,and FGF2 is a promising potential therapeutic target during IAV infection.展开更多
Interleukin-17(IL-17),a member of the IL-17 cytokine family,plays a crucial role in mediating the immune response against extracellular bacteria and fungi in the lung.Although there is increasing evidence that IL-17 i...Interleukin-17(IL-17),a member of the IL-17 cytokine family,plays a crucial role in mediating the immune response against extracellular bacteria and fungi in the lung.Although there is increasing evidence that IL-17 is involved in protective immunity against H1 and H3 influenza virus infections,little is known about the role of IL-17 in the highly pathogenic H5N1 influenza virus infection.In this study,we show that H5N1-infected IL-17 knockout(KO)mice exhibit markedly increased weight loss,more pronounced lung immunopathology and significantly reduced survival rates as compared with infected wild-type controls.Moreover,the frequency of B cells in the lung were substantially decreased in IL-17 KO mice after virus infection,which correlated with reduced CXCR5 expression in B cells and decreased CXCL13 production in the lung tissue of IL-17 KO mice.Consistent with this observation,B cells from IL-17 KO mice exhibited a significant reduction in chemokine-mediated migration in culture.Taken together,these findings demonstrate a critical role for IL-17 in mediating the recruitment of B cells to the site of pulmonary influenza virus infection in mice.展开更多
Background:Influenza B virus can cause epidemics with high pathogenicity, so it poses a serious threat to public health. A feature representation algorithm is proposed in this paper to identify the pathogenicity pheno...Background:Influenza B virus can cause epidemics with high pathogenicity, so it poses a serious threat to public health. A feature representation algorithm is proposed in this paper to identify the pathogenicity phenotype of influenza B virus.Methods:The dataset included all 11 influenza virus proteins encoded in eight genome segments of 1724 strains. Two types of features were hierarchically used to build the prediction model. Amino acid features were directly delivered from 67 feature descriptors and input into the random forest classifier to output informative features about the class label and probabilistic prediction. The sequential forward search strategy was used to optimize the informative features. The final features for each strain had low dimensions and included knowledge from different perspectives, which were used to build the machine learning model for pathogenicity identification.Results:The 40 signature positions were achieved by entropy screening. Mutations at position 135 of the hemagglutinin protein had the highest entropy value (1.06). After the informative features were directly generated from the 67 random forest models, the dimensions for class and probabilistic features were optimized as 4 and 3, respectively. The optimal class features had a maximum accuracy of 94.2% and a maximum Matthews correlation coefficient of 88.4%, while the optimal probabilistic features had a maximum accuracy of 94.1% and a maximum Matthews correlation coefficient of 88.2%. The optimized features outperformed the original informative features and amino acid features from individual descriptors. The sequential forward search strategy had better performance than the classical ensemble method.Conclusions:The optimized informative features had the best performance and were used to build a predictive model so as to identify the phenotype of influenza B virus with high pathogenicity and provide early risk warning for disease control.展开更多
基金National"863 Project"(2006AA02Z409)National health project(200802023)Yunnan sciences and technology cooperation(2006XY29)
文摘Due to the insufficient supply of embryonated chicken eggs,the preparation of large quantities of inactivated influenza vaccines will require an alternative virus culture system after the emergence or reemergence of a pandemic influenza virus.The Vero cell is one of the ideal options since it was used for producing many kinds of human vaccines.However,most of the influenza viruses can not grow well in Vero cells.To develop a new influenza vaccine with Vero cells as a substrate,the virus needs to adapt to this cell substrate to maintain high growth characteristics.By serial passages in Vero cells,the B/Yunnan/2/2005va(B)strain was successfully adapted to Vero cells,with the hemagglutination titer(HAT)of the virus reaching 1:512.The high growth characteristic of this strain is stable up to 21 passages.The strain was identified by hemagglutination inhibition (HAI)test and sequencing respectively;the HA1 gene sequence of the virus was cloned and analyzed.The screening and establishment of high growth B virus provides an important tool for influenza vaccine production in Vero cells.
文摘BACKGROUND Among the various types and causes of mesenteric ischemia,superior mesenteric vein(SMV)thrombosis is a rare and ambiguous disease.If a patient presents with SMV thrombosis,past medical history should be reviewed,and the patient should be screened for underlying disease.SMV thrombosis may also occur due to systemic infection.In this report,we describe a case of SMV thrombosis complicated by influenza B infection.CASE SUMMARY A 64-year-old male visited the hospital with general weakness,muscle aches,fever,and abdominal pain.The patient underwent computed tomography(CT)and was diagnosed with SMV thrombosis.Since the patient’s muscle pain and fever could not be explained by the SMV thrombosis,the clinician performed a test for influenza,which produced a positive result for influenza B.The patient had a thrombus in the SMV only,with no invasion of the portal or splenic veins,and was clinically stable.Anticoagulation treatment was prescribed without surgery or other procedures.The follow-up CT scan showed improvement,and the patient was subsequently discharged with continued oral anticoagulant treatment.CONCLUSION This case provides evidence that influenza may be a possible risk factor for SMV thrombosis.If unexplained abdominal pain is accompanied by an influenza infection,examination of an abdominal CT scan may be necessary to screen for possible SMV thrombosis.
基金National Science Foundation of China(U1805231)National Program for Innovation and Entrepreneurship Training of University Students(202110389008)+2 种基金Special Fund Project for Scientific and Technological Innovation of Fujian Agriculture and Forestry University(CXZX2018015,CXZX2020060A)Key Laboratory Project of Animal Infectious Disease Control and Biotechnology in Fujian Province(2018KF03)National Science Foundation of Fujian Province(2020J01539).
文摘Neuromedin B(NMB)is a member of mammalian bombesin-like peptide family and almost all its potent biological actions take place exclusively through its receptor NMBR,which has been identified as a G-protein couple receptor with seven trans-membrane regions.NMB and NMBR represent an interesting signaling axis over which NMB/NMBR perform multiple biological activities,in particularly,they have been highlighted in the regulation of the immunology system.This review aims to provide a brief overview of the recent advancements in our understanding regarding the potential immunological functions of NMB and NMBR in cell proliferation,tumorigenesis,angiogenesis,neurogenic inflammation,anti-influenza A virus(IAV)infections,and briefly discusses the potential importance of these observations.All these implicated that targeting NMBR or developing analogues of NMB may represent a useful strategy for development of new anti-IAV agents.
基金supported by the Chinese National Natural Science Foundation of China(grant number:31970502)the National Key Research and Development Program of China(2021YFC2301701,2020ZX10001-016-003 and ZX10304402-003-006).
文摘Taurolidine(TRD),a derivative of taurine,has anti-bacterial and anti-tumor effects by chemically reacting with cell-walls,endotoxins and exotoxins to inhibit the adhesion of microorganisms.However,its application in antiviral therapy is seldom reported.Here,we reported that TRD significantly inhibited the replication of influenza virus H5N1 in MDCK cells with the half-maximal inhibitory concentration(EC_(50))of 34.45μg/mL.Furthermore,the drug inhibited the amplification of the cytokine storm effect and improved the survival rate of mice lethal challenged with H5N1(protection rate was 86%).Moreover,TRD attenuated virus-induced lung damage and reduced virus titers in mice lungs.Administration of TRD reduced the number of neutrophils and increased the number of lymphocytes in the blood of H5N1 virus-infected mice.Importantly,the drug regulated the NF-κB signaling pathway by inhibiting the separation of NF-κB and IκBa,thereby reducing the expression of inflammatory factors.In conclusion,our findings suggested that TRD could act as a potential anti-influenza drug candidate in further clinical studies.
基金partially supported by the National Research Program of the Ministry of Science and Technology of the People’s Republic of China(2016YFA0600104)donations from Delos Living LLC and the Cyrus Tang Foundation to Tsinghua University.
文摘Annual influenza B virus epidemics and outbreaks cause severe influenza diseases in humans and pose a threat to public health. China is an important epidemic area of influenza B viruses. However, the spatial, temporal transmission pathways and the demography history of influenza B viruses in China remain unknown. We collected the haemagglutinin gene sequences sampled of influenza B virus in China between 1973 and 2018. A Bayesian Markov chain Monte Carlo phylogeographic discrete approach was used to infer the spatial and temporal phylodynamics of influenza B virus. The Bayesian phylogeographic analysis of influenza B viruses showed that the North subtropical and South subtropical zones are the origins of the Victoria and Yamagata lineage viruses, respectively. Furthermore, the South temperate and North subtropical zones acted as transition nodes in the Victoria lineage virus dispersion network and that the North subtropical and Mid subtropical zones acted as transition nodes in the Yamagata lineage virus dispersion network. Our findings contribute to the knowledge regarding the spatial and temporal patterns of influenza B virus outbreaks in China.
文摘Background: During the coronavirus disease 2019(COVID-19)pandemic,seasonal influenza activity declined globally and remained below previous seasonal levels,but intensified in China since 2021.Preventive measures to COVID-19 accompanied by different epidemic characteristics of influenza in different regions of the world.To better respond to influenza outbreaks under the COVID-19 pandemic,we analyzed the epidemiology,antigenic and genetic characteristics,and antiviral susceptibility of influenza viruses in the mainland of China during 2020–2021.Methods: Respiratory specimens from influenza like illness cases were collected by sentinel hospitals and sent to network laboratories in Chinese National Influenza Surveillance Network.Antigenic mutation analysis of influenza virus isolates was performed by hemagglutination inhibition assay.Next-generation sequencing was used for genetic analyses.We also conducted molecular characterization and phylogenetic analysis of circulating influenza viruses.Viruses were tested for resistance to antiviral medications using phenotypic and/or sequence-based methods.Results: In the mainland of China,influenza activity recovered in 2021 compared with that in 2020 and intensified during the traditional influenza winter season,but it did not exceed the peak in previous years.Almost all viruses isolated during the study period were of the B/Victoria lineage and were characterized by genetic diversity,with the subgroup 1A.3a.2 viruses currently predominated.37.8%viruses tested were antigenically similar to reference viruses representing the components of the vaccine for the 2020–2021 and 2021–2022 Northern Hemisphere influenza seasons.In addition,China has a unique subgroup of 1A.3a.1 viruses.All viruses tested were sensitive to neuraminidase inhibitors and endonuclease inhibitors,except two B/Victoria lineage viruses identified to have reduced sensitivity to neuraminidase inhibitors.Conclusions: Influenza activity increased in the mainland of China in 2021,and caused flu season in the winter of 2021–2022.Although the diversity of influenza(sub)type decreases,B/Victoria lineage viruses show increased genetic and antigenic diversity.The world needs to be fully prepared for the co-epidemic of influenza and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus globally.
基金supported by the National Science and Technology Major Project of the Ministry of Science and Technology of China (2012ZX10004501-004-001) The Science & Technology project of Urumqi of Xinjiang Uygur Autonomous Region (Y151310010): Study on the mechanism of anti-influenza virus effect of compound Yi-Zhi-Hao Pellets
文摘As a leading cause of respiratory disease, influenza A virus(IAV) presents a pandemic threat in annual seasonal outbreaks. Given the limitation of existing anti-influenza therapies, there remains to be a requirement for new drugs. Compound Yi-Zhi-Hao pellet(CYZH) is a famous traditional Chinese medicine(TCM) used in the clinic, whose formula has been recorded in Complication of National Standard for Traditional Chinese Medicine to treat common cold. In this study, we found that CYZH exhibited a broad-spectrum anti-influenza activity and inhibited the expression of viral RNA and proteins in vitro. Mechanistically, CYZH had no inhibitory activities against viral protein hemagglutinin and IAV RNA-dependent RNA polymerase. Instead, it induced activation of erythroid 2-related factor 2(Nrf2) and nuclear factor kappa B(NF-κB), which subsequently upregulated heme oxygenase-1(HO-1) expression.Also, CYZH protected cells from oxidative damage induced by reactive oxygen series. In conclusions,CYZH inhibits IAV replication in vitro, at least partly by activating expression of the Nrf2/HO-1 pathway.
基金funding from the National High Technology Research and Development Program of China (SS2015AA020924)the National Natural Science Foundation of China (81771700)+2 种基金the Ministry of Science and Technology of China (2013ZXI0004003 and SS2012AA020905)the National Major Research and Development Program (2016YFA0502203 and 2017YFC1200800)P.Y.was supported by the Beijing Nova Program (Z141107001814054).
文摘Influenza virus (IAV)infection is a major cause of severe respiratory illness that affects almost every country in the world.IAV infections result in respiratory illness and even acute lung injury and death,but the underlying mechanisms responsible for IAV pathogenesis have not yet been fully elucidated.In this study,the basic fibroblast growth factor 2 (FGF2)level was markedly increased in H1N1 virus-infected humans and mice.FGF2,which is predominately derived from epithelial cells,recruits and activates neutrophils via the FGFR2-PI3K-AKT-NFKB signaling pathway.FGF2 depletion or knockout exacerbated influenzaassociated disease by impairing neutrophil recruitment and activation.More importantly,administration of the recombinant FGF2 protein significantly aUeviated the severity of IAV-induced lung injury and promoted the survival of IAV-infected mice.Based on the results from experiments in which neutrophils were depleted and adoptively transferred,FGF2 protected mice against IAV , infection by recruiting neutrophils.Thus,FGF2 plays a critical role in preventing IAV-induced lung injury,and FGF2 is a promising potential therapeutic target during IAV infection.
基金supported by the Research Fund for the Control of Infectious Diseases(RFCID),Food and Health Bureau,Hong Kong SAR Government(No.10091002).
文摘Interleukin-17(IL-17),a member of the IL-17 cytokine family,plays a crucial role in mediating the immune response against extracellular bacteria and fungi in the lung.Although there is increasing evidence that IL-17 is involved in protective immunity against H1 and H3 influenza virus infections,little is known about the role of IL-17 in the highly pathogenic H5N1 influenza virus infection.In this study,we show that H5N1-infected IL-17 knockout(KO)mice exhibit markedly increased weight loss,more pronounced lung immunopathology and significantly reduced survival rates as compared with infected wild-type controls.Moreover,the frequency of B cells in the lung were substantially decreased in IL-17 KO mice after virus infection,which correlated with reduced CXCR5 expression in B cells and decreased CXCL13 production in the lung tissue of IL-17 KO mice.Consistent with this observation,B cells from IL-17 KO mice exhibited a significant reduction in chemokine-mediated migration in culture.Taken together,these findings demonstrate a critical role for IL-17 in mediating the recruitment of B cells to the site of pulmonary influenza virus infection in mice.
文摘Background:Influenza B virus can cause epidemics with high pathogenicity, so it poses a serious threat to public health. A feature representation algorithm is proposed in this paper to identify the pathogenicity phenotype of influenza B virus.Methods:The dataset included all 11 influenza virus proteins encoded in eight genome segments of 1724 strains. Two types of features were hierarchically used to build the prediction model. Amino acid features were directly delivered from 67 feature descriptors and input into the random forest classifier to output informative features about the class label and probabilistic prediction. The sequential forward search strategy was used to optimize the informative features. The final features for each strain had low dimensions and included knowledge from different perspectives, which were used to build the machine learning model for pathogenicity identification.Results:The 40 signature positions were achieved by entropy screening. Mutations at position 135 of the hemagglutinin protein had the highest entropy value (1.06). After the informative features were directly generated from the 67 random forest models, the dimensions for class and probabilistic features were optimized as 4 and 3, respectively. The optimal class features had a maximum accuracy of 94.2% and a maximum Matthews correlation coefficient of 88.4%, while the optimal probabilistic features had a maximum accuracy of 94.1% and a maximum Matthews correlation coefficient of 88.2%. The optimized features outperformed the original informative features and amino acid features from individual descriptors. The sequential forward search strategy had better performance than the classical ensemble method.Conclusions:The optimized informative features had the best performance and were used to build a predictive model so as to identify the phenotype of influenza B virus with high pathogenicity and provide early risk warning for disease control.
