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APOBEC3 基因复杂多样性揭示翼手目蝙蝠中抗逆转录病毒限制因子的差异进化。

Differential Evolution of Antiretroviral Restriction Factors in Pteropid Bats as Revealed by APOBEC3 Gene Complexity.

机构信息

Health Security Program, Life Sciences Discipline, Burnet Institute, Melbourne, VIC, Australia.

Department of Microbiology, Monash University, Clayton, VIC, Australia.

出版信息

Mol Biol Evol. 2018 Jul 1;35(7):1626-1637. doi: 10.1093/molbev/msy048.

Abstract

Bats have attracted attention in recent years as important reservoirs of viruses deadly to humans and other mammals. These infections are typically nonpathogenic in bats raising questions about innate immune differences that might exist between bats and other mammals. The APOBEC3 gene family encodes antiviral DNA cytosine deaminases with important roles in the suppression of diverse viruses and genomic parasites. Here, we characterize pteropid APOBEC3 genes and show that species within the genus Pteropus possess the largest and most diverse array of APOBEC3 genes identified in any mammal reported to date. Several bat APOBEC3 proteins are antiviral as demonstrated by restriction of retroviral infectivity using HIV-1 as a model, and recombinant A3Z1 subtypes possess strong DNA deaminase activity. These genes represent the first group of antiviral restriction factors identified in bats with extensive diversification relative to homologues in other mammals.

摘要

近年来,蝙蝠作为对人类和其他哺乳动物具有致命性的病毒的重要宿主而受到关注。这些感染在蝙蝠中通常是非致病性的,这引发了人们对蝙蝠与其他哺乳动物之间可能存在固有免疫差异的疑问。APOBEC3 基因家族编码抗病毒 DNA 胞嘧啶脱氨酶,在抑制多种病毒和基因组寄生虫方面发挥着重要作用。在这里,我们对翼手目 APOBEC3 基因进行了表征,并表明在迄今为止报道的任何哺乳动物中,属于 Pteropus 属的物种拥有最大和最多样化的 APOBEC3 基因。几种蝙蝠 APOBEC3 蛋白具有抗病毒作用,这是通过使用 HIV-1 作为模型来限制逆转录病毒感染性来证明的,并且重组 A3Z1 亚型具有很强的 DNA 脱氨酶活性。这些基因是在蝙蝠中发现的第一组抗病毒限制因子,与其他哺乳动物的同源物相比,它们具有广泛的多样化。

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