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Human ANP32A/B are SUMOylated and utilized by avian influenza virus NS2 protein to overcome species-specific restriction

文献类型: 外文期刊

作者: Liuke Sun;Xing Guo;Mengmeng Yu;Xue Feng Wang;Huiling Ren;Xiaojun Wang

作者机构:

关键词: ANP32A/B;; SUMOylation; Avian influenza virus

期刊名称: Nature Communications

ISSN: 2041-1723

年卷期: 2025 年 15 卷 1 期

页码:

收录情况: SCIE(2024版)

摘要: Human ANP32A/B (huANP32A/B) poorly support the polymerase activity of avian influenza viruses (AIVs), thereby limiting interspecies transmission of AIVs from birds to humans. The SUMO-interacting motif (SIM) within NS2 promotes the adaptation of AIV polymerase to huANP32A/B via a yet undisclosed mechanism. Here we show that huANP32A/B are SUMOylated by the E3 SUMO ligase PIAS2α, and deSUMOylated by SENP1. SUMO modification of huANP32A/B results in the recruitment of NS2, thereby facilitating huANP32A/B-supported AIV polymerase activity. Such a SUMO-dependent recruitment of NS2 is mediated by its association with huANP32A/B via the SIM-SUMO interaction module, where K68/K153-SUMO in huANP32A or K68/K116-SUMO in huANP32B interacts with the NS2-SIM. The SIM-SUMO-mediated interactions between NS2 and huANP32A/B function to promote AIV polymerase activity by positively regulating AIV vRNP-huANP32A/B interactions and AIV vRNP assembly. Our study offers insights into the mechanism of NS2-SIM in facilitating AIVs adaptation to mammals.

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