宿主蛋白ANP32A对流感病毒功能影响的研究进展

doi:10.16431/j.cnki.1671-7236.2021.09.035

摘要/Abstract

摘要： 流感病毒是一类危害人和动物健康的RNA病毒，其在宿主细胞内的有效复制离不开宿主蛋白酸性核磷蛋白32家族成员A （ANP32A）和病毒RNA聚合酶的协助和支持。病毒RNA聚合酶由3种蛋白PB1、PB2和PA组成，且ANP32A与病毒RNA聚合酶的最强相互作用需要这3种蛋白的共同参与。ANP32A是酸性富含亮氨酸的核磷蛋白32（ANP32）家族成员，其被确认为支持细胞核中病毒RNA聚合酶活性的关键宿主因子，对流感病毒的复制具有重要的作用。ANP32A的物种特异性差异决定了病毒RNA聚合酶的宿主范围：独特的33个氨基酸序列存在于禽类ANP32A （avANP32A），而在哺乳动物ANP32A中缺乏此氨基酸序列。avANP32A中特有的33个氨基酸序列能增强ANP32A的功能，从而增加禽源特征流感病毒聚合酶活性。禽流感病毒（Avian influenza virus，AIV）不能有效利用较短的ANP32A （即缺乏独特33个氨基酸序列的ANP32A），因而哺乳动物ANP32A无法支持禽源特征聚合酶活性，然而在人ANP32A （huANP32A）中插入这33个氨基酸能促进其对AIV聚合酶的支持作用。此外，流感病毒的适应性突变也能增强AIV在哺乳动物中的传播力和致病性。AIV适应哺乳动物时往往会发生E627K突变，以增强其在哺乳动物中的复制能力。作者主要介绍了宿主蛋白ANP32A对流感病毒复制、转录的影响和流感病毒发生适应性突变的作用机制，简要论述了ANP32A与聚合酶的相互作用对流感病毒跨物种感染的分子机制。

关键词: 流感病毒; ANP32A; 流感病毒聚合酶

Abstract: Influenza virus is a kind of RNA virus which is harmful to human and animal health. Its effective replication in host cells cannot be achieved without the assistance and support of host protein acidic nuclear phosphoprotein 32 family member A (ANP32A) and virus RNA polymerase. Viral RNA polymerase consists of three proteins:PB1, PB2 and PA, and the strongest interaction between ANP32A and viral RNA polymerase requires the participation of these three proteins. ANP32A is a member of the acidic leucine-rich nuclear phosphoprotein 32 (ANP32) family. It has been identified as a key host factor supporting the activity of viral RNA polymerase in the nucleus and plays an important role in Influenza virus replication. The species-specific difference of ANP32A determines the host range of viral RNA polymerase:A unique 33 amino acid sequence exists in avian ANP32A (avANP32A), but lacks this amino acid sequence in mammalian ANP32A. The 33 amino acid sequences unique to avANP32A can enhance the function of ANP32A, thus increasing the polymerase activity of Avian influenza virus (AIV). AIV cannot make effective use of short ANP32A (that is, ANP32A lacking a unique 33 amino acid sequence), so mammalian ANP32A cannot support avian characteristic polymerase activity. However, inserting these 33 amino acids into human ANP32A (huANP32A) can promote its support for AIV polymerase. Adaptive mutation of Influenza virus can also enhance the transmission and pathogenicity of AIV in mammals. E627K mutation often occurs when AIV adapts to mammals to enhance its replication ability in mammals. This review mainly introduced the effect of host protein ANP32A on replication and transcription of Influenza virus and the mechanism of adaptive mutation of Influenza virus, and briefly discussed the molecular mechanism of the interaction between ANP32A and polymerase on Influenza virus cross-species infection.

Key words: Influenza virus; ANP32A; Influenza virus polymerase

中图分类号:

S852.65

张晓璇, 郭晶, 李旭勇. 宿主蛋白ANP32A对流感病毒功能影响的研究进展[J]. 中国畜牧兽医, 2021, 48(9): 3432-3437.

ZHANG Xiaoxuan, GUO Jing, LI Xuyong. Research Progress on the Effect of Host Protein ANP32A on Influenza Virus Function[J]. China Animal Husbandry and Veterinary Medicine, 2021, 48(9): 3432-3437.

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