Mutations in the polymerase basic 2(PB2) gene of avian influenza viruses are important signatures for their adaptation to mammalian hosts. Various adaptive mutations have been identified around the 627 and nuclear loc...Mutations in the polymerase basic 2(PB2) gene of avian influenza viruses are important signatures for their adaptation to mammalian hosts. Various adaptive mutations have been identified around the 627 and nuclear localization sequence(NLS) domains of PB2 protein, and these mutations contribute to the replicative ability of avian influenza viruses.However, few studies have focused on adaptive mutations in other regions of PB2. In this study, we investigated the functional roles of the D253N mutation in PB2 in an H9N2 virus. This mutation was found to affect an amino acid residue in the middle domain of the PB2 protein. The virus with the D253N mutation showed higher polymerase activity and transiently increased viral replication in human cells. However, the mutant did not show significant differences in viral replication in the respiratory tract of mice upon infection. Our results supported that the D253N mutation in the middle domain of PB2, similar to mutations at the 627 and NLS domains, specifically contributed to the replication of avian influenza viruses in human cells.展开更多
Both global warming and influenza trouble humans in varying ways, therefore it is important to study the trends in both global warming and evolution of influenza A virus, in particular, proteins from influenza A virus...Both global warming and influenza trouble humans in varying ways, therefore it is important to study the trends in both global warming and evolution of influenza A virus, in particular, proteins from influenza A virus. Recently, we have conducted two studies along this line to determine the trends between global warming and polymerase acidic protein as well as matrix protein 2. Although these two studies reveal some interesting findings, many studies are still in need because at least there are ten different proteins in influenza A virus. In this study, we analyze the trends in global warming and evolution of polymerase basic protein 2 (PB2) from influenza A virus. The PB2 evolution from 1956 to 2008 was defined using the unpredictable portion of aminoacid pair. Then the trend in this evolution was compared with the trend in the global temperature, the temperature in north and south hemispheres, and the temperature in influenza A virus sampling site and species carrying influenza A virus. The results show the similar trends in global warming and in PB2 evolution, which are in good agreement with our previous studies in polymerase acidic protein and matrix protein 2 from influenza A virus.展开更多
TypeⅠinterferon(IFN)-mediated innate immune responses represent the first line of host defense against viral infection.However,the molecular mechanisms by which avian infuenza virus(AIV)inhibits typeⅠIFN production ...TypeⅠinterferon(IFN)-mediated innate immune responses represent the first line of host defense against viral infection.However,the molecular mechanisms by which avian infuenza virus(AIV)inhibits typeⅠIFN production in ducks are not well understood.Here,we frst found that the polymerase basic 2(PB2)protein of H5N1 subtype AIV inhibited the typeⅠIFN responses by targeting duck mitochondrial antiviral signaling protein(MAVS).We further demonstrated that H5N1-PB2 bound to theΔtransmembrane(ΔTM)domain of duck MAVS,and the polymerase basic 1(PB1)binding domain(PBD)and RNA binding nuclear import domain(RND)of H5N1-PB2 interacted with MAVS to inhibit typeⅠIFN expression in ducks.Collectively,our fndings contribute to understanding the molecular mechanism by which AIV proteins regulate the retinoic acid-inducible geneⅠ(RIG-Ⅰ)-like receptor(RLR)signaling pathway to evade host antiviral immune responses in ducks.展开更多
目的了解广东省甲型H1N1pdm流感病毒聚合酶碱性蛋白2(polymerase basic protein 2,PB2)基因变异株的分子特征,探讨其特异性分子位点,为流感病毒防控提供科学依据。方法采集感染PB2基因变异株的2例病例咽拭子标本进行病毒分离,并挑选23...目的了解广东省甲型H1N1pdm流感病毒聚合酶碱性蛋白2(polymerase basic protein 2,PB2)基因变异株的分子特征,探讨其特异性分子位点,为流感病毒防控提供科学依据。方法采集感染PB2基因变异株的2例病例咽拭子标本进行病毒分离,并挑选23株广东省流感病毒株进行测序分析,利用GISAID提供的参考序列和疫苗株序列对血凝素(hemagglutinin,HA)和PB2基因进行进化分析;开展毒株抗原分析和神经氨酸酶(neuraminidase,NA)抑制试验;构建PB2蛋白模型,分析聚合酶活性。结果PB2-D701N和PB2-A271S变异株HA基因出现H399N氨基酸位点突变,均属于6B.1A.5a.2a分支;与疫苗株A/Victoria/4897/2022同属大分支不同小分支,均为疫苗类似株。在三维结构中,PB2-D701N和PB2-A271S突变发生电荷改变和亲疏水变化。结论PB2-D701和A271高度保守,PB2突变株尚未成为优势株,但其抗原性与疫苗匹配性高,对NA抑制剂敏感。三维模型推测,PB2-D701N突变可增强病毒的致病力而影响传播能力,PB2-A271S则可能影响流感病毒的聚合酶活性和聚合酶复合物的合成。展开更多
基金supported by the Science Research Project of the Guangdong Province (Grant no. 2016A050503047)Health and Medical Research Fund (Grant No. 12111832)+1 种基金Guangzhou Medical University High Level University Construction Project FundingResearch Grants Council of the Hong Kong Special Administrative Region, China, through the Theme Based Research Scheme (Ref: T11-705/14N)
文摘Mutations in the polymerase basic 2(PB2) gene of avian influenza viruses are important signatures for their adaptation to mammalian hosts. Various adaptive mutations have been identified around the 627 and nuclear localization sequence(NLS) domains of PB2 protein, and these mutations contribute to the replicative ability of avian influenza viruses.However, few studies have focused on adaptive mutations in other regions of PB2. In this study, we investigated the functional roles of the D253N mutation in PB2 in an H9N2 virus. This mutation was found to affect an amino acid residue in the middle domain of the PB2 protein. The virus with the D253N mutation showed higher polymerase activity and transiently increased viral replication in human cells. However, the mutant did not show significant differences in viral replication in the respiratory tract of mice upon infection. Our results supported that the D253N mutation in the middle domain of PB2, similar to mutations at the 627 and NLS domains, specifically contributed to the replication of avian influenza viruses in human cells.
文摘Both global warming and influenza trouble humans in varying ways, therefore it is important to study the trends in both global warming and evolution of influenza A virus, in particular, proteins from influenza A virus. Recently, we have conducted two studies along this line to determine the trends between global warming and polymerase acidic protein as well as matrix protein 2. Although these two studies reveal some interesting findings, many studies are still in need because at least there are ten different proteins in influenza A virus. In this study, we analyze the trends in global warming and evolution of polymerase basic protein 2 (PB2) from influenza A virus. The PB2 evolution from 1956 to 2008 was defined using the unpredictable portion of aminoacid pair. Then the trend in this evolution was compared with the trend in the global temperature, the temperature in north and south hemispheres, and the temperature in influenza A virus sampling site and species carrying influenza A virus. The results show the similar trends in global warming and in PB2 evolution, which are in good agreement with our previous studies in polymerase acidic protein and matrix protein 2 from influenza A virus.
基金supported by the grants from the National Natural Science Foundation of China(31872497 and 32072844)the National Key Research and Development Program of China(2021YFD1800200 and 2016YFD0500207)the Laboratory of Lingnan Modern Agriculture Project,China(NT2021007)。
文摘TypeⅠinterferon(IFN)-mediated innate immune responses represent the first line of host defense against viral infection.However,the molecular mechanisms by which avian infuenza virus(AIV)inhibits typeⅠIFN production in ducks are not well understood.Here,we frst found that the polymerase basic 2(PB2)protein of H5N1 subtype AIV inhibited the typeⅠIFN responses by targeting duck mitochondrial antiviral signaling protein(MAVS).We further demonstrated that H5N1-PB2 bound to theΔtransmembrane(ΔTM)domain of duck MAVS,and the polymerase basic 1(PB1)binding domain(PBD)and RNA binding nuclear import domain(RND)of H5N1-PB2 interacted with MAVS to inhibit typeⅠIFN expression in ducks.Collectively,our fndings contribute to understanding the molecular mechanism by which AIV proteins regulate the retinoic acid-inducible geneⅠ(RIG-Ⅰ)-like receptor(RLR)signaling pathway to evade host antiviral immune responses in ducks.
文摘目的了解广东省甲型H1N1pdm流感病毒聚合酶碱性蛋白2(polymerase basic protein 2,PB2)基因变异株的分子特征,探讨其特异性分子位点,为流感病毒防控提供科学依据。方法采集感染PB2基因变异株的2例病例咽拭子标本进行病毒分离,并挑选23株广东省流感病毒株进行测序分析,利用GISAID提供的参考序列和疫苗株序列对血凝素(hemagglutinin,HA)和PB2基因进行进化分析;开展毒株抗原分析和神经氨酸酶(neuraminidase,NA)抑制试验;构建PB2蛋白模型,分析聚合酶活性。结果PB2-D701N和PB2-A271S变异株HA基因出现H399N氨基酸位点突变,均属于6B.1A.5a.2a分支;与疫苗株A/Victoria/4897/2022同属大分支不同小分支,均为疫苗类似株。在三维结构中,PB2-D701N和PB2-A271S突变发生电荷改变和亲疏水变化。结论PB2-D701和A271高度保守,PB2突变株尚未成为优势株,但其抗原性与疫苗匹配性高,对NA抑制剂敏感。三维模型推测,PB2-D701N突变可增强病毒的致病力而影响传播能力,PB2-A271S则可能影响流感病毒的聚合酶活性和聚合酶复合物的合成。
