蜱虫的一个祖先 ANP32 基因座产生了多种蛋白质变体,它们都支持 Thogoto 病毒聚合酶

Zhenyu Zhang, Thomas Nipper, Ishmael D Aziati, Adrianus Boon, Andrew Mehle
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引用次数: 0

摘要

病毒聚合酶依赖细胞辅助因子来支持病毒基因的高效转录和病毒基因组的复制。流感病毒这种正粘病毒的 RNA 依赖性 RNA 聚合酶需要细胞 ANP32A 或 ANP32B 蛋白才能进行基因组复制。然而,人们对其他正粘病毒(如蜱传吸血病毒)是否需要 ANP32 蛋白知之甚少。最近的结构研究和功能测试表明,Thogoto 病毒聚合酶同时使用来自棕狗蜱的 ANP32A 和 ANP32B。我们在此澄清,这种蜱载体只编码一个与 ANP32A 相对应的 ANP32 基因座。这个单一基因通过替代剪接和起始位点选择产生多种蛋白质变体,所有这些都会增强 Thogoto 病毒聚合酶的能力。人和鸡的 ANP32 蛋白也能增强 Thogoto 病毒聚合酶的活性。因此,ANP32A 是一种深度保守的病毒辅助因子,Thogoto 病毒利用相隔近 10 亿年进化的 ANP32 同源物显示出显著的可塑性。
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A single ancestral ANP32 locus in ticks creates multiple protein variants that all support the Thogoto virus polymerase
Viral polymerases rely on cellular cofactors to support efficient transcription of viral genes and replication of the viral genome. The RNA-dependent RNA polymerase of influenza virus, an orthomyxovirus, requires cellular ANP32A or ANP32B proteins for genome replication. However, little is known about whether ANP32 proteins are required by other orthomyxoviruses like the tick-borne thogotoviruses. Recent structural studies coupled with functional assays suggested that the Thogoto virus polymerase uses both ANP32A and ANP32B from brown dog ticks. We clarify here that this tick vector encodes a single ANP32 locus corresponding to ANP32A. This single gene produces multiple protein variants through alternative splicing and start-site selection, all of which enhance Thogoto virus polymerase. Thogoto virus polymerase activity is also enhanced by human and chicken ANP32 proteins. Thus, ANP32A is a deeply conserved pro-viral cofactor and Thogoto virus shows remarkable plasticity utilizing ANP32 homologues separated by almost 1 billion years of evolution.
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