聚合酶
生物
RNA剪接
H5N1亚型流感病毒
遗传学
外显子
病毒学
核糖核酸
病毒
基因
作者
Steven F. Baker,Mitchell P. Ledwith,Andrew Mehle
出处
期刊:Cell Reports
[Elsevier]
日期:2018-09-01
卷期号:24 (10): 2581-2588.e4
被引量:66
标识
DOI:10.1016/j.celrep.2018.08.012
摘要
Adaptation of viruses to their hosts can result in specialization and a restricted host range. Species-specific polymorphisms in the influenza virus polymerase restrict its host range during transmission from birds to mammals. ANP32A was recently identified as a cellular co-factor affecting polymerase adaption and activity. Avian influenza polymerases require ANP32A containing an insertion resulting from an exon duplication uniquely encoded in birds. Here we find that natural splice variants surrounding this exon create avian ANP32A proteins with distinct effects on polymerase activity. We demonstrate species-independent direct interactions between all ANP32A variants and the PB2 polymerase subunit. This interaction is enhanced in the presence of viral genomic RNA. In contrast, only avian ANP32A restored ribonucleoprotein complex assembly for a restricted polymerase by enhancing RNA synthesis. Our data suggest that ANP32A splicing variation among birds differentially affects viral replication, polymerase adaption, and the potential of avian hosts to be reservoirs.
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