HIV-1 co-receptor tropism is central for understanding the transmission and pathogenesis of HIV-1 infection. We performed a genome-wide comparison between the adaptive evolution of R5 and X4 variants from HIV-1 subtyp...HIV-1 co-receptor tropism is central for understanding the transmission and pathogenesis of HIV-1 infection. We performed a genome-wide comparison between the adaptive evolution of R5 and X4 variants from HIV-1 subtypes B and C. The results showed that R5 and X4 variants experienced differential evolutionary patterns and different HIV-1 genes encountered various positive selection pressures, suggesting that complex selection pressures are driving HIV-1 evolution. Compared with other hypervariable regions of Gp120, significantly more positively selected sites were detected in the V3 region of subtype B X4 variants, V2 region of subtype B R5 variants, and V1 and V4 regions of subtype C X4 variants, indicating an association of positive selection with co-receptor recognition/binding. Intriguingly, a significantly higher proportion (33.3% and 55.6%, P【0.05) of positively selected sites were identified in the C3 region than other conserved regions of Gp120 in all the analyzed HIV-1 variants, indicating that the C3 region might be more important to HIV-1 adaptation than previously thought. Approximately half of the positively selected sites identified in the env gene were identical between R5 and X4 variants. There were three common positively selected sites (96, 113 and 281) identified in Gp41 of all X4 and R5 variants from subtypes B and C. These sites might not only suggest a functional importance in viral survival and adaptation, but also imply a potential cross-immunogenicity between HIV-1 R5 and X4 variants, which has important implications for AIDS vaccine development.展开更多
He and his colleagues[1]reported identification of the mobile resistance genes tet(X3)and tet(X4)on conjugative plasmids in Enterobacteriaceae and Acinetobacter isolated in China recently published in Nature Microbiol...He and his colleagues[1]reported identification of the mobile resistance genes tet(X3)and tet(X4)on conjugative plasmids in Enterobacteriaceae and Acinetobacter isolated in China recently published in Nature Microbiology.They noted that both tet(X3)and tet(X4)can confer resistance to tigecycline and the newly FDA-approved eravacycline and omadacyclin,which are last-resort antibiotics used to treat multi-drug-resistant(MDR)bacterial infections.Our previous report[2]revealed that live poultry market(LPM)is a huge antibiotic resistance gene(ARG)reservoir,including the mobile colistin resistance(mcr)genes,mcr-1,mcr-3,mcr-4 and mcr-5.Large-scale metagenomic data screening showed that tigecycline resistance gene tet(X3)was widespread in poultry faecal samples collected from China LPMs,whereas it has not been detected in human(n=2019)gut microbiomes[3],which suggested that tet(X3)is previously confined to animal guts or animal-derived bacteria.展开更多
Background The genome of the severe acute respiratory syndrome-associated coronavirus ( SARS-CoV) includes sequences encoding the putative protein X4 ( ORF8, ORF7a), consisting of 122 amino acids. The deduced sequence...Background The genome of the severe acute respiratory syndrome-associated coronavirus ( SARS-CoV) includes sequences encoding the putative protein X4 ( ORF8, ORF7a), consisting of 122 amino acids. The deduced sequence contains a probable cleaved signal peptide sequence and a C-terminal transmembrane helix, indicating that protein X4 is likely to be a type I membrane protein. This study was conducted to demonstrate whether the protein X4 was expressed and its essential function in the process of SARS-CoV infection. Methods The prokaryotic and eukaryotic protein X4-expressing plasmids were constructed. Recombinant soluble protein X4 was purified from E. coli using ion exchange chromatography, and the preparation was injected into chicken for rising specific polyclonal antibodies. The expression of protein X4 in SARS-CoV infected Vero E6 cells and lung tissues from patients with SARS was performed using immunofluorescence assay and immunohistochemistry technique. The preliminary function of protein X4 was evaluated by treatment with and over-expression of protein X4 in cell lines. Western blot was employed to evaluate the expression of protein X4 in SARS-CoV particles. Results We expressed and purified soluble recombinant protein X4 from E. coli, and generated specific antibodies against protein X4. Western blot proved that the protein X4 was not assembled in the SARS-CoV particles. Indirect immunofluorescence assays revealed that the expression of protein X4 was detected at 8 hours after infection in SARS-CoV-infected Vero E6 cells. It was also detected in the tung tissues from patients with SARS. Treatment with and overexpression of protein X4 inhibited the growth of Balb/c 313 cells as determined by cell counting and MTT assays. Conclusion The results provide the evidence of protein X4 expression following SARS-CoV infection, and may facilitate further investigation of the immunopathological mechanism of SARS.展开更多
测试地点:中国·上海市·松江豪华中级SUV轿跑车,BMW以X4又一次开发出一个全新的细分市场!它会取得和X6一样的成功吗?作为过去30年提升最为迅速的高端豪华汽车品牌,BMW对如何扩张产品线一直有独到见解。这个以"纯粹驾驶乐...测试地点:中国·上海市·松江豪华中级SUV轿跑车,BMW以X4又一次开发出一个全新的细分市场!它会取得和X6一样的成功吗?作为过去30年提升最为迅速的高端豪华汽车品牌,BMW对如何扩张产品线一直有独到见解。这个以"纯粹驾驶乐趣"为Slogan的品牌,始终坚持旗下所有产品必须能给消费者带来卓越的公路驾驶感受,而至于这款车到底是跑车、轿车、SUV还是Crossover,反倒好像并不那么重要。所以当1999年推出第一款SUV车型X 5时,B M W将其定义为运动型休旅车(SAV)。展开更多
基金supported by the National Natural Science Foundation of China (Grant No. 30600352)the "Top-notch Personnel" Project of Ji-angsu University, the National Basic Research Program of China (Grant No. 2006CB504200)the Open Research Fund Program of the State Key Laboratory of Virology of China (Grant No. 2009008)
文摘HIV-1 co-receptor tropism is central for understanding the transmission and pathogenesis of HIV-1 infection. We performed a genome-wide comparison between the adaptive evolution of R5 and X4 variants from HIV-1 subtypes B and C. The results showed that R5 and X4 variants experienced differential evolutionary patterns and different HIV-1 genes encountered various positive selection pressures, suggesting that complex selection pressures are driving HIV-1 evolution. Compared with other hypervariable regions of Gp120, significantly more positively selected sites were detected in the V3 region of subtype B X4 variants, V2 region of subtype B R5 variants, and V1 and V4 regions of subtype C X4 variants, indicating an association of positive selection with co-receptor recognition/binding. Intriguingly, a significantly higher proportion (33.3% and 55.6%, P【0.05) of positively selected sites were identified in the C3 region than other conserved regions of Gp120 in all the analyzed HIV-1 variants, indicating that the C3 region might be more important to HIV-1 adaptation than previously thought. Approximately half of the positively selected sites identified in the env gene were identical between R5 and X4 variants. There were three common positively selected sites (96, 113 and 281) identified in Gp41 of all X4 and R5 variants from subtypes B and C. These sites might not only suggest a functional importance in viral survival and adaptation, but also imply a potential cross-immunogenicity between HIV-1 R5 and X4 variants, which has important implications for AIDS vaccine development.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29010000)the External Cooperation Program of CAS(153211KYSB20160001).
文摘He and his colleagues[1]reported identification of the mobile resistance genes tet(X3)and tet(X4)on conjugative plasmids in Enterobacteriaceae and Acinetobacter isolated in China recently published in Nature Microbiology.They noted that both tet(X3)and tet(X4)can confer resistance to tigecycline and the newly FDA-approved eravacycline and omadacyclin,which are last-resort antibiotics used to treat multi-drug-resistant(MDR)bacterial infections.Our previous report[2]revealed that live poultry market(LPM)is a huge antibiotic resistance gene(ARG)reservoir,including the mobile colistin resistance(mcr)genes,mcr-1,mcr-3,mcr-4 and mcr-5.Large-scale metagenomic data screening showed that tigecycline resistance gene tet(X3)was widespread in poultry faecal samples collected from China LPMs,whereas it has not been detected in human(n=2019)gut microbiomes[3],which suggested that tet(X3)is previously confined to animal guts or animal-derived bacteria.
文摘Background The genome of the severe acute respiratory syndrome-associated coronavirus ( SARS-CoV) includes sequences encoding the putative protein X4 ( ORF8, ORF7a), consisting of 122 amino acids. The deduced sequence contains a probable cleaved signal peptide sequence and a C-terminal transmembrane helix, indicating that protein X4 is likely to be a type I membrane protein. This study was conducted to demonstrate whether the protein X4 was expressed and its essential function in the process of SARS-CoV infection. Methods The prokaryotic and eukaryotic protein X4-expressing plasmids were constructed. Recombinant soluble protein X4 was purified from E. coli using ion exchange chromatography, and the preparation was injected into chicken for rising specific polyclonal antibodies. The expression of protein X4 in SARS-CoV infected Vero E6 cells and lung tissues from patients with SARS was performed using immunofluorescence assay and immunohistochemistry technique. The preliminary function of protein X4 was evaluated by treatment with and over-expression of protein X4 in cell lines. Western blot was employed to evaluate the expression of protein X4 in SARS-CoV particles. Results We expressed and purified soluble recombinant protein X4 from E. coli, and generated specific antibodies against protein X4. Western blot proved that the protein X4 was not assembled in the SARS-CoV particles. Indirect immunofluorescence assays revealed that the expression of protein X4 was detected at 8 hours after infection in SARS-CoV-infected Vero E6 cells. It was also detected in the tung tissues from patients with SARS. Treatment with and overexpression of protein X4 inhibited the growth of Balb/c 313 cells as determined by cell counting and MTT assays. Conclusion The results provide the evidence of protein X4 expression following SARS-CoV infection, and may facilitate further investigation of the immunopathological mechanism of SARS.
文摘测试地点:中国·上海市·松江豪华中级SUV轿跑车,BMW以X4又一次开发出一个全新的细分市场!它会取得和X6一样的成功吗?作为过去30年提升最为迅速的高端豪华汽车品牌,BMW对如何扩张产品线一直有独到见解。这个以"纯粹驾驶乐趣"为Slogan的品牌,始终坚持旗下所有产品必须能给消费者带来卓越的公路驾驶感受,而至于这款车到底是跑车、轿车、SUV还是Crossover,反倒好像并不那么重要。所以当1999年推出第一款SUV车型X 5时,B M W将其定义为运动型休旅车(SAV)。
