人类免疫缺陷病毒1型(Human immunodeficiency virus type 1,HIV-1)是人获得性免疫缺陷综合征即艾滋病(AIDS)的病原,HIV-1感染人类免疫细胞,渐进性地破坏免疫系统,最终引发艾滋病。ANP32A (酸性核磷蛋白32A)与ANP32B同属于ANP32蛋白家族...人类免疫缺陷病毒1型(Human immunodeficiency virus type 1,HIV-1)是人获得性免疫缺陷综合征即艾滋病(AIDS)的病原,HIV-1感染人类免疫细胞,渐进性地破坏免疫系统,最终引发艾滋病。ANP32A (酸性核磷蛋白32A)与ANP32B同属于ANP32蛋白家族,是近几年新发现的与流感病毒复制相关的宿主蛋白。前期有研究证明宿主因子ANP32A/B是A型流感病毒聚合酶发挥功能所必需的宿主因子,并揭示了其与聚合酶相互作用的关键位点,为新型抗流感药物及转基因动物的研发提供了有效靶点(Zhang H et al. Journal of Virology 2019)。展开更多
Host ANP32 family proteins are crucial for maintaining the activity of influenza RNA polymerase and play an important role in the cross-species transmission of influenza viruses.To date,the molecular properties of equ...Host ANP32 family proteins are crucial for maintaining the activity of influenza RNA polymerase and play an important role in the cross-species transmission of influenza viruses.To date,the molecular properties of equine ANP32(eqANP32)protein are poorly understood,particularly the mechanisms that affect equine influenza virus(EIV)RNA polymerase activity.Here,we found that there are six alternative splicing variants of equine ANP32A(eqANP32A)with different levels of expression.Further studies showed that these six splicing variants of eqANP32A supported the activity of EIV RNA polymerase to varying degrees,with the variant eqANP32A_X2 having the highest expression abundance and exhibiting the highest support of polymerase activity.Sequence analysis demonstrated that the differences in the N-Cap regions of the six splicing variants significantly affected their N-terminal conformation,but did not affect their ability to bind RNA polymerase.We also demonstrated that there is only one transcript of eqANP32B,and that this transcript showed only very low support to the EIV RNA polymerase.This functional defect in eqANP32B is caused by the sequence of the 110–259 amino acids at its Cterminus.Our results indicated that it is the eqANP32A_X2 protein that mainly determines the efficiency of the EIV replication in horses.In conclusion,our study parsed the molecular properties of eqANP32 family proteins and revealed the sequence features of eqANP32A and eqANP32B,suggesting for the first time that the N-Cap region of ANP32A protein also plays an important role in supporting the activity of the influenza virus polymerase.展开更多
文摘人类免疫缺陷病毒1型(Human immunodeficiency virus type 1,HIV-1)是人获得性免疫缺陷综合征即艾滋病(AIDS)的病原,HIV-1感染人类免疫细胞,渐进性地破坏免疫系统,最终引发艾滋病。ANP32A (酸性核磷蛋白32A)与ANP32B同属于ANP32蛋白家族,是近几年新发现的与流感病毒复制相关的宿主蛋白。前期有研究证明宿主因子ANP32A/B是A型流感病毒聚合酶发挥功能所必需的宿主因子,并揭示了其与聚合酶相互作用的关键位点,为新型抗流感药物及转基因动物的研发提供了有效靶点(Zhang H et al. Journal of Virology 2019)。
基金the National Natural Science Foundation of China to HL Zhang(32002275)Natural Science Foundation of Heilongjiang Province of China to HL Zhang(YQ2020C021).
文摘Host ANP32 family proteins are crucial for maintaining the activity of influenza RNA polymerase and play an important role in the cross-species transmission of influenza viruses.To date,the molecular properties of equine ANP32(eqANP32)protein are poorly understood,particularly the mechanisms that affect equine influenza virus(EIV)RNA polymerase activity.Here,we found that there are six alternative splicing variants of equine ANP32A(eqANP32A)with different levels of expression.Further studies showed that these six splicing variants of eqANP32A supported the activity of EIV RNA polymerase to varying degrees,with the variant eqANP32A_X2 having the highest expression abundance and exhibiting the highest support of polymerase activity.Sequence analysis demonstrated that the differences in the N-Cap regions of the six splicing variants significantly affected their N-terminal conformation,but did not affect their ability to bind RNA polymerase.We also demonstrated that there is only one transcript of eqANP32B,and that this transcript showed only very low support to the EIV RNA polymerase.This functional defect in eqANP32B is caused by the sequence of the 110–259 amino acids at its Cterminus.Our results indicated that it is the eqANP32A_X2 protein that mainly determines the efficiency of the EIV replication in horses.In conclusion,our study parsed the molecular properties of eqANP32 family proteins and revealed the sequence features of eqANP32A and eqANP32B,suggesting for the first time that the N-Cap region of ANP32A protein also plays an important role in supporting the activity of the influenza virus polymerase.
