In June 2013,the fi rst human H6N1 infl uenza virus infec-tion was confirmed in Taiwan.However,the origin and molecular characterization of this virus,A/Taiwan/2/2013(H6N1),have not been well studied thus far.In the p...In June 2013,the fi rst human H6N1 infl uenza virus infec-tion was confirmed in Taiwan.However,the origin and molecular characterization of this virus,A/Taiwan/2/2013(H6N1),have not been well studied thus far.In the present report,we performed phylogenetic and coalescent analy-ses of this virus and compared its molecular profi le/char-acteristics with other closely related strains.Molecular characterization of H6N1 revealed that it is a typical avian infl uenza virus of low pathogenicity,which might not rep-licate and propagate well in the upper airway in mammals.Phylogenetic analysis revealed that the virus clusters with A/chicken/Taiwan/A2837/2013(H6N1)in seven genes,except PB1.For the PB1 gene,A/Taiwan/2/2013 was clus-tered with a different H6N1 lineage from A/chicken/Taiwan/A2837/2013.Although a previous study demonstrated that the PB2,PA,and M genes of A/Taiwan/2/2013 might be derived from the H5N2 viruses,coalescent analyses revealed that these H5N2 viruses were derived from more recent strains than that of the ancestor of A/Taiwan/2/2013.Therefore,we propose that A/Taiwan/2/2013 is a reassor-tant from different H6N1 lineages circulating in chickens in Taiwan.Furthermore,compared to avian isolates,a sin-gle P186L(H3 numbering)substitution in the hemaggluti-nin H6 of the human isolate might increase the mammali-an receptor binding and,hence,this strain’s pathogenicity in humans.Overall,human infection with this virus seems an accidental event and is unlikely to cause an infl uenza pandemic.However,its co-circulation and potential reas-sortment with other infl uenza subtypes are still worthy of attention.展开更多
Avian infl uenza A virus continues to pose a global threat with occasional H5N1 human infections,which is em-phasized by a recent severe human infection caused by avian-origin H7N9 in China.Luckily these viruses do no...Avian infl uenza A virus continues to pose a global threat with occasional H5N1 human infections,which is em-phasized by a recent severe human infection caused by avian-origin H7N9 in China.Luckily these viruses do not transmit effi ciently in human populations.With a few ami-no acid substitutions of the hemagglutinin H5 protein in the laboratory,two H5 mutants have been shown to obtain an air-borne transmission in a mammalian ferret model.Here in this study one of the mutant H5 proteins devel-oped by Kawaoka’s group(VN1203mut)was expressed in a baculovirus system and its receptor-binding properties were assessed.We herein show that the VN1203mut had a dramatically reduced binding affi nity for the avianα2,3-linkage receptor compared to wild type but showed no detectable increase in affi nity for the humanα2,6-linkage receptor,using Surface Plasmon Resonance techonology.Further,the crystal structures of the VN1203mut and its complexes with either human or avian receptors demon-strate that the VN1203mut binds the human receptor in the same binding manner(cis conformation)as seen for the HAs of previously reported 1957 and 1968 pandemic influenza viruses.Our receptor binding and crystallo-graphic data shown here further confi rm that the ability to bind the avian receptor has to decrease for a higher hu-man receptor binding affi nity.As the Q226L substitution is shown important for obtaining human receptor binding,we suspect that the newly emerged H7N9 binds human receptor as H7 has a Q226L substitution.展开更多
Background:Respiratory morbidity of former preterm infants and especially those with bronchopulmonary dysplasia(BPD)is high during infancy and early childhood.Data sources:We performed a review based on a literature s...Background:Respiratory morbidity of former preterm infants and especially those with bronchopulmonary dysplasia(BPD)is high during infancy and early childhood.Data sources:We performed a review based on a literature search including EMBASE,MEDLINE,and CINAHL databases to identify all relevant papers published in the English and German literature on influenza and respiratory syncytial virus infection associated with preterm infant,prematurity,and BPD between 1980 and 2014.Results:Recurrent respiratory symptoms remain common at preschool age,school age and even into young adulthood.Acute viral respiratory tract infections due to different pathogens cause significant morbidity and necessitate rehospitalizations during the fi rst years of life.Infl uenza virus infection plays a minor role compared to respiratory syncytial virus(RSV)associated respiratory tract infection during infancy and early childhood.Nevertheless,particular morbidity to both viruses is high.Conclusions:The particular burden of both viral diseases in preterm infants is dominated by RSV and its associated rehospitalizations during the fi rst two years of life.Prophylactic measures include vaccination against influenza virus of family members and caregivers and active immunization starting at the age of 6 months,and monthly injections of palivizumab during the cold season to avoid severe RSV disease and its sequelae.展开更多
基金the National Basic Research Pro-gram(973 Program)(Nos.2010CB530303,2011CB504703,and 2012CB955501an intramural special grant for influenza virus research from the Chinese Academy of Sciences(KSZD-EW-Z-002)the Doctoral Starting up Foundation of Taishan Medical College.GFG is a leading principal investigator of the Innova-tive Research Group of the National Natural Science Foundation of China(Grant No.81021003)。
文摘In June 2013,the fi rst human H6N1 infl uenza virus infec-tion was confirmed in Taiwan.However,the origin and molecular characterization of this virus,A/Taiwan/2/2013(H6N1),have not been well studied thus far.In the present report,we performed phylogenetic and coalescent analy-ses of this virus and compared its molecular profi le/char-acteristics with other closely related strains.Molecular characterization of H6N1 revealed that it is a typical avian infl uenza virus of low pathogenicity,which might not rep-licate and propagate well in the upper airway in mammals.Phylogenetic analysis revealed that the virus clusters with A/chicken/Taiwan/A2837/2013(H6N1)in seven genes,except PB1.For the PB1 gene,A/Taiwan/2/2013 was clus-tered with a different H6N1 lineage from A/chicken/Taiwan/A2837/2013.Although a previous study demonstrated that the PB2,PA,and M genes of A/Taiwan/2/2013 might be derived from the H5N2 viruses,coalescent analyses revealed that these H5N2 viruses were derived from more recent strains than that of the ancestor of A/Taiwan/2/2013.Therefore,we propose that A/Taiwan/2/2013 is a reassor-tant from different H6N1 lineages circulating in chickens in Taiwan.Furthermore,compared to avian isolates,a sin-gle P186L(H3 numbering)substitution in the hemaggluti-nin H6 of the human isolate might increase the mammali-an receptor binding and,hence,this strain’s pathogenicity in humans.Overall,human infection with this virus seems an accidental event and is unlikely to cause an infl uenza pandemic.However,its co-circulation and potential reas-sortment with other infl uenza subtypes are still worthy of attention.
基金the National Basic Research Program(973 Program)(No.2011CB504703)the National Natural Sci-ence Foundation of China(Grant No.81290342).G.F.G.is a leading principal investigator of the NSFC Innovative Research Group(Grant No.81021003)。
文摘Avian infl uenza A virus continues to pose a global threat with occasional H5N1 human infections,which is em-phasized by a recent severe human infection caused by avian-origin H7N9 in China.Luckily these viruses do not transmit effi ciently in human populations.With a few ami-no acid substitutions of the hemagglutinin H5 protein in the laboratory,two H5 mutants have been shown to obtain an air-borne transmission in a mammalian ferret model.Here in this study one of the mutant H5 proteins devel-oped by Kawaoka’s group(VN1203mut)was expressed in a baculovirus system and its receptor-binding properties were assessed.We herein show that the VN1203mut had a dramatically reduced binding affi nity for the avianα2,3-linkage receptor compared to wild type but showed no detectable increase in affi nity for the humanα2,6-linkage receptor,using Surface Plasmon Resonance techonology.Further,the crystal structures of the VN1203mut and its complexes with either human or avian receptors demon-strate that the VN1203mut binds the human receptor in the same binding manner(cis conformation)as seen for the HAs of previously reported 1957 and 1968 pandemic influenza viruses.Our receptor binding and crystallo-graphic data shown here further confi rm that the ability to bind the avian receptor has to decrease for a higher hu-man receptor binding affi nity.As the Q226L substitution is shown important for obtaining human receptor binding,we suspect that the newly emerged H7N9 binds human receptor as H7 has a Q226L substitution.
文摘Background:Respiratory morbidity of former preterm infants and especially those with bronchopulmonary dysplasia(BPD)is high during infancy and early childhood.Data sources:We performed a review based on a literature search including EMBASE,MEDLINE,and CINAHL databases to identify all relevant papers published in the English and German literature on influenza and respiratory syncytial virus infection associated with preterm infant,prematurity,and BPD between 1980 and 2014.Results:Recurrent respiratory symptoms remain common at preschool age,school age and even into young adulthood.Acute viral respiratory tract infections due to different pathogens cause significant morbidity and necessitate rehospitalizations during the fi rst years of life.Infl uenza virus infection plays a minor role compared to respiratory syncytial virus(RSV)associated respiratory tract infection during infancy and early childhood.Nevertheless,particular morbidity to both viruses is high.Conclusions:The particular burden of both viral diseases in preterm infants is dominated by RSV and its associated rehospitalizations during the fi rst two years of life.Prophylactic measures include vaccination against influenza virus of family members and caregivers and active immunization starting at the age of 6 months,and monthly injections of palivizumab during the cold season to avoid severe RSV disease and its sequelae.
