Respiratory syncytial virus(RSV)is a significant cause of acute lower respiratory tract infection(ALRTI)in children underfive years of age.Between 2017 and 2021,396 complete sequences of the RSV F gene were obtained fro...Respiratory syncytial virus(RSV)is a significant cause of acute lower respiratory tract infection(ALRTI)in children underfive years of age.Between 2017 and 2021,396 complete sequences of the RSV F gene were obtained from 500 RSV-positive throat swabs collected from ten hospitals across nine provinces in China.In addition,151 sequences from China were sourced from GenBank and GISAID,making a total of 549 RSV F gene sequences subjected to analysis.Phylogenetic and genetic diversity analyses revealed that the RSV F genes circulating in China from 2017 to 2021 have remained relatively conserved,although some amino acids(AAs)have undergone changes.AA mutations with frequencies10%were identified at six sites and the p27 region:V384I(site I),N276S(site II),R213S(siteØ),and K124N(p27)for RSV A;F45L(site I),M152I/L172Q/S173 L/I185V/K191R(site V),and R202Q/I206M/Q209R(siteØ)for RSV B.Comparing mutational frequencies in RSV-F before and after 2020 revealed minor changes for RSV A,while the K191R,I206M,and Q209R frequencies increased by over 10%in RSV B.Notably,the nirsevimab-resistant mutation,S211N in RSV B,increased in frequency from 0%to 1.15%.Both representative strains aligned with the predicted RSV-F structures of their respective prototypes exhibited similar conformations,with low root-mean-square deviation values.These results could provide foundational data from China for the development of RSV mAbs and vaccines.展开更多
Human respiratory syncytial virus(RSV)is a severe threat to children and a main cause of acute lower respiratory tract infections.Nevertheless,the intra-host evolution and inter-regional diffusion of RSV are little kn...Human respiratory syncytial virus(RSV)is a severe threat to children and a main cause of acute lower respiratory tract infections.Nevertheless,the intra-host evolution and inter-regional diffusion of RSV are little known.In this study,we performed a systematic surveillance in hospitalized children in Hubei during 2020–2021,in which 106 RSV-positive samples were detected both clinically and by metagenomic next generation sequencing(mNGS).RSV-A and RSV-B groups co-circulated during surveillance with RSV-B being predominant.About 46 high-quality genomes were used for further analyses.A total of 163 intra-host nucleotide variation(iSNV)sites distributed in 34 samples were detected,and glycoprotein(G)gene was the most enriched gene for iSNVs,with non-synonymous substitutions more than synonymous substitutions.Evolutionary dynamic analysis showed that the evolutionary rates of G and NS2 genes were higher,and the population size of RSV groups changed over time.We also found evidences of inter-regional diffusion from Europe and Oceania to Hubei for RSV-A and RSV-B,respectively.This study highlighted the intra-host and inter-host evolution of RSV,and provided some evi-dences for understanding the evolution of RSV.展开更多
Background Respiratory syncytial virus （RSV） is a common pathogen in the lower respiratory tract of infants and children. Recent studies have shown that in adults, especially in the eldedy population who have relati...Background Respiratory syncytial virus （RSV） is a common pathogen in the lower respiratory tract of infants and children. Recent studies have shown that in adults, especially in the eldedy population who have relatively weak immunity, lower respiratory tract infection is not uncommon. RSV was detected in 22% hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease （COPD）, and the detection rate was only next to that of parvovirus and influenza virus respectively. Further studies revealed that lung infection of RSV could lead to inflammatory destruction and structural remodeling. This study was undertaken to examine the effect of infection with RSV on matrix metalloproteinase （MMPs） in mice, and to explore the role of RSV in the pathogenesis of pulmonary diseases. Methods Twenty BALB/c mice were divided randomly into an RSV infection group and a blank control group. The mice in the RSV infection group were given 100 pl liquid containing 10s PFU of RSV by intranasal instillation. Three days after the infection, the bronchoalveolar lavage fluid （BALF） was harvested and RT-PCR and Western blotting were used to detect MMP-9 and the expression of tissue inhibitors of matdx metalloproteinase （TIMP）-I mRNA in lung tissues. Gelatin zymography was employed to detect the activities of MMP-9 and MMP-2 in BALF. Immunohistochemistry was used to determine the expressions of E-cadherin （E-cd） and proliferating call nuclear antigen （PCNA） in the lung tissues. Results In the BALF of the mice infected with RSV, the activities of MMP-9 and MMP-2 were significantly increased （t=-6.08, P〈0.01 and t=5.68, P〈0.01）. The levels of mRNAand proteins of MMP-9 in the lung tissues of the mica infected with RSV were significantly elevated, and the mRNA and protein levels were significantly higher than those of the blank controls. Though the ratio of MMP-9/TIMP-1 mRNA in the lung tissues of the infected mica was not significantly different from that of the normal controls, the ratio of the MMP-9/TIMP-1 protein in the RSV infection group was significantly higher than that in the control group. Moreover, the number of cells with positive E-cd expression was decreased and the number of calls positive for PCNA was increased, with an enhanced expression. Conclusions In mica, infection with RSV can significantly increase the activities of MMP-9 and MMP-2, and conspicuously elevate the mRNA transcription of MMP-9. RSV infection can increase the activity of gelatinase while up-regulating its inhibitory factors but increase its protein ratio of MMP-9/TIMP-1 in lung tissues, thereby facilitating fibrosis after structural destruction of the airway. The resultant status might be an important factor causing chronic reconstruction of the airway.展开更多
基金supported by the National Key Research and Development Program of China(grant number 2023YFC2306002)National Science and Technology Major Projects(grant number 2017ZX10104001-005-010)CAMS Innovation Fund for Medical Sciences(CIFMS)(Grant Number 2019-I2M-5-026)and Funding for Reform and Development of Beijing Municipal Health Commission.
文摘Respiratory syncytial virus(RSV)is a significant cause of acute lower respiratory tract infection(ALRTI)in children underfive years of age.Between 2017 and 2021,396 complete sequences of the RSV F gene were obtained from 500 RSV-positive throat swabs collected from ten hospitals across nine provinces in China.In addition,151 sequences from China were sourced from GenBank and GISAID,making a total of 549 RSV F gene sequences subjected to analysis.Phylogenetic and genetic diversity analyses revealed that the RSV F genes circulating in China from 2017 to 2021 have remained relatively conserved,although some amino acids(AAs)have undergone changes.AA mutations with frequencies10%were identified at six sites and the p27 region:V384I(site I),N276S(site II),R213S(siteØ),and K124N(p27)for RSV A;F45L(site I),M152I/L172Q/S173 L/I185V/K191R(site V),and R202Q/I206M/Q209R(siteØ)for RSV B.Comparing mutational frequencies in RSV-F before and after 2020 revealed minor changes for RSV A,while the K191R,I206M,and Q209R frequencies increased by over 10%in RSV B.Notably,the nirsevimab-resistant mutation,S211N in RSV B,increased in frequency from 0%to 1.15%.Both representative strains aligned with the predicted RSV-F structures of their respective prototypes exhibited similar conformations,with low root-mean-square deviation values.These results could provide foundational data from China for the development of RSV mAbs and vaccines.
基金National Key Research and Development Program of China(2018YFC1603803)National Natural Science Foun-dation of China(31970548)+2 种基金Knowledge Innovation Program of Wuhan-Basi Research(2022020801010519)Health Commission of Hubei Province(WJ 2021M262)Natural Science Fund of Hubei Province(2021CFA012).
文摘Human respiratory syncytial virus(RSV)is a severe threat to children and a main cause of acute lower respiratory tract infections.Nevertheless,the intra-host evolution and inter-regional diffusion of RSV are little known.In this study,we performed a systematic surveillance in hospitalized children in Hubei during 2020–2021,in which 106 RSV-positive samples were detected both clinically and by metagenomic next generation sequencing(mNGS).RSV-A and RSV-B groups co-circulated during surveillance with RSV-B being predominant.About 46 high-quality genomes were used for further analyses.A total of 163 intra-host nucleotide variation(iSNV)sites distributed in 34 samples were detected,and glycoprotein(G)gene was the most enriched gene for iSNVs,with non-synonymous substitutions more than synonymous substitutions.Evolutionary dynamic analysis showed that the evolutionary rates of G and NS2 genes were higher,and the population size of RSV groups changed over time.We also found evidences of inter-regional diffusion from Europe and Oceania to Hubei for RSV-A and RSV-B,respectively.This study highlighted the intra-host and inter-host evolution of RSV,and provided some evi-dences for understanding the evolution of RSV.
文摘Background Respiratory syncytial virus （RSV） is a common pathogen in the lower respiratory tract of infants and children. Recent studies have shown that in adults, especially in the eldedy population who have relatively weak immunity, lower respiratory tract infection is not uncommon. RSV was detected in 22% hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease （COPD）, and the detection rate was only next to that of parvovirus and influenza virus respectively. Further studies revealed that lung infection of RSV could lead to inflammatory destruction and structural remodeling. This study was undertaken to examine the effect of infection with RSV on matrix metalloproteinase （MMPs） in mice, and to explore the role of RSV in the pathogenesis of pulmonary diseases. Methods Twenty BALB/c mice were divided randomly into an RSV infection group and a blank control group. The mice in the RSV infection group were given 100 pl liquid containing 10s PFU of RSV by intranasal instillation. Three days after the infection, the bronchoalveolar lavage fluid （BALF） was harvested and RT-PCR and Western blotting were used to detect MMP-9 and the expression of tissue inhibitors of matdx metalloproteinase （TIMP）-I mRNA in lung tissues. Gelatin zymography was employed to detect the activities of MMP-9 and MMP-2 in BALF. Immunohistochemistry was used to determine the expressions of E-cadherin （E-cd） and proliferating call nuclear antigen （PCNA） in the lung tissues. Results In the BALF of the mice infected with RSV, the activities of MMP-9 and MMP-2 were significantly increased （t=-6.08, P〈0.01 and t=5.68, P〈0.01）. The levels of mRNAand proteins of MMP-9 in the lung tissues of the mica infected with RSV were significantly elevated, and the mRNA and protein levels were significantly higher than those of the blank controls. Though the ratio of MMP-9/TIMP-1 mRNA in the lung tissues of the infected mica was not significantly different from that of the normal controls, the ratio of the MMP-9/TIMP-1 protein in the RSV infection group was significantly higher than that in the control group. Moreover, the number of cells with positive E-cd expression was decreased and the number of calls positive for PCNA was increased, with an enhanced expression. Conclusions In mica, infection with RSV can significantly increase the activities of MMP-9 and MMP-2, and conspicuously elevate the mRNA transcription of MMP-9. RSV infection can increase the activity of gelatinase while up-regulating its inhibitory factors but increase its protein ratio of MMP-9/TIMP-1 in lung tissues, thereby facilitating fibrosis after structural destruction of the airway. The resultant status might be an important factor causing chronic reconstruction of the airway.
