Dear Editor,In March 2013,the first 3 cases of severe disease dueto a novel avian-origin influenza A(H7N9)virus weredetected in the Chinese provinces of Shanghai and Anhui(Gao R,et al.,2013).A total of 339 laboratory-...Dear Editor,In March 2013,the first 3 cases of severe disease dueto a novel avian-origin influenza A(H7N9)virus weredetected in the Chinese provinces of Shanghai and Anhui(Gao R,et al.,2013).A total of 339 laboratory-confirmedcases with 100 deaths were reported until January 142014(WHO,2014).To the best of our knowledge,thisis the first time that human infection with the avian in-fluenza A H7N9 subtype has been detected.Prior to展开更多
Human influenza viruses preferentially bind to sialic acid-α2,6-galactose (SAα2,6Gal) receptors, which are predominant in human upper respiratory epithelia, whereas avian influenza viruses preferentially bind to SA...Human influenza viruses preferentially bind to sialic acid-α2,6-galactose (SAα2,6Gal) receptors, which are predominant in human upper respiratory epithelia, whereas avian influenza viruses preferentially bind to SAα2,3Gal receptors. However, variants with amino acid substitutions around the receptor-binding sites of the hemagglutinin (HA) protein can be selected after several passages of human influenza viruses from patients’ respiratory samples in the allantoic cavities of embryonated chicken eggs. In this study, we detected an egg-adapted HA S190R mutation in the pandemic H1N1 virus 2009 (pdmH1N1), and evaluated the effects of this mutation on receptor binding affinity and pathogenicity in mice. Our results revealed that residue 190 is located within the pocket structure of the receptor binding site. The single mutation to arginine at position 190 slightly increased the binding affinity of the virus to the avian receptor and decreased its binding to the long human α2,6-linked sialic acid receptor. Our study demonstrated that the S190R mutation resulted in earlier death and higher weight loss in mice compared with the wild-type virus. Higher viral titers at 1 dpi (days post infection) and diffuse damage at 4 dpi were observed in the lung tissues of mice infected with the mutant virus.展开更多
The onsite next generation sequencing(NGS)of Ebola virus(EBOV)genomes during the 2013–2016 Ebola epidemic in Western Africa provides an opportunity to trace the origin,transmission,and evolution of this virus.Herein,...The onsite next generation sequencing(NGS)of Ebola virus(EBOV)genomes during the 2013–2016 Ebola epidemic in Western Africa provides an opportunity to trace the origin,transmission,and evolution of this virus.Herein,we have diagnosed a cohort of EBOV patients in Sierra Leone in 2015,during the late phase of the outbreak.The surviving EBOV patients had a recovery process characterized by decreasing viremia,fever,and biochemical parameters.EBOV genomes sequenced through the longitudinal blood samples of these patients showed dynamic intra-host substitutions of the virus during acute infection,including the previously described short stretches of 13 serial TNC mutations.Remarkably,within individual patients,samples collected during the early phase of infection possessed Ts at these nucleotide sites,whereas they were replaced by Cs in samples collected in the later phase,suggesting that these short stretches of TNC mutations could emerge independently.In addition,up to a total of 35 nucleotide sites spanning the EBOV genome were mutated coincidently.Our study showed the dynamic intra-host adaptation of EBOV during patient recovery and gave more insight into the complex EBOV-host interactions.展开更多
基金supported by an Emergency Research Project on human infection with avian influenza H7N9 virus from the National Ministry of Science and Technology(No.KJYJ-201301-01 to Dr.Shu)the National Basic Research Program(973)of China(grant No.2011CB504704 to Dr.Shu)China Mega-Project for Infectious Disease(2013ZX10004-101)
文摘Dear Editor,In March 2013,the first 3 cases of severe disease dueto a novel avian-origin influenza A(H7N9)virus weredetected in the Chinese provinces of Shanghai and Anhui(Gao R,et al.,2013).A total of 339 laboratory-confirmedcases with 100 deaths were reported until January 142014(WHO,2014).To the best of our knowledge,thisis the first time that human infection with the avian in-fluenza A H7N9 subtype has been detected.Prior to
基金supported by the National Key Research and Development Program of China(2016YFC1200201 to Yuelong Shu)the National Mega-projects for Infectious Diseases(2014ZX10004002002 to Yuelong Shu)the young scientist fund of Chinese Center for Disease Control and Prevention(2016A103 to Wenfei Zhu)
文摘Human influenza viruses preferentially bind to sialic acid-α2,6-galactose (SAα2,6Gal) receptors, which are predominant in human upper respiratory epithelia, whereas avian influenza viruses preferentially bind to SAα2,3Gal receptors. However, variants with amino acid substitutions around the receptor-binding sites of the hemagglutinin (HA) protein can be selected after several passages of human influenza viruses from patients’ respiratory samples in the allantoic cavities of embryonated chicken eggs. In this study, we detected an egg-adapted HA S190R mutation in the pandemic H1N1 virus 2009 (pdmH1N1), and evaluated the effects of this mutation on receptor binding affinity and pathogenicity in mice. Our results revealed that residue 190 is located within the pocket structure of the receptor binding site. The single mutation to arginine at position 190 slightly increased the binding affinity of the virus to the avian receptor and decreased its binding to the long human α2,6-linked sialic acid receptor. Our study demonstrated that the S190R mutation resulted in earlier death and higher weight loss in mice compared with the wild-type virus. Higher viral titers at 1 dpi (days post infection) and diffuse damage at 4 dpi were observed in the lung tissues of mice infected with the mutant virus.
基金supported by the Megaproject for Infectious Disease Research of China(2016ZX10004222-003)the research of Ebola pathogen from the National Natural Science Foundation of China(NSFC,81590763)+4 种基金National Key Research and Development Program of China(2016YFC1200200 to Y.Shu)the Distinguished Young Scientist Program of the NSFC(81525017 to Y.Shu)the Excellent Young Scientist Program of the NSFC(81822040 to W.J.Liu)the Taishan Scholar Project of Shandong Province(ts201511056 to W.Shi)G.F.Gao is a primary principal investigator of the NSFC Innovative Research Group(81621091).
文摘The onsite next generation sequencing(NGS)of Ebola virus(EBOV)genomes during the 2013–2016 Ebola epidemic in Western Africa provides an opportunity to trace the origin,transmission,and evolution of this virus.Herein,we have diagnosed a cohort of EBOV patients in Sierra Leone in 2015,during the late phase of the outbreak.The surviving EBOV patients had a recovery process characterized by decreasing viremia,fever,and biochemical parameters.EBOV genomes sequenced through the longitudinal blood samples of these patients showed dynamic intra-host substitutions of the virus during acute infection,including the previously described short stretches of 13 serial TNC mutations.Remarkably,within individual patients,samples collected during the early phase of infection possessed Ts at these nucleotide sites,whereas they were replaced by Cs in samples collected in the later phase,suggesting that these short stretches of TNC mutations could emerge independently.In addition,up to a total of 35 nucleotide sites spanning the EBOV genome were mutated coincidently.Our study showed the dynamic intra-host adaptation of EBOV during patient recovery and gave more insight into the complex EBOV-host interactions.