KPNA6 is a Cofactor of ANP32A/B in Supporting Influenza Virus Polymerase Activity.
KPNA6 is a Cofactor of ANP32A/B in Supporting Influenza Virus Polymerase Activity.
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KPNA 6是支持流感病毒聚合酶活性的ANP 32 A/B的辅因子。
DOI：
10.1128/spectrum.02073-21
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发表时间：
2022-02-23
影响因子：
3.7
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Yu M;Sun L;Zhang Z;Zhang Y;Zhang H;Na L;Wang X
甲型流感病毒（Influenza A virus，IAV）RNA依赖性RNA聚合酶（RNA-dependent RNA polymerase，vPol）是由PB 2、PB 1和PA组成的异源三聚体，与vRNA和核蛋白（Nucleoprotein，NP）形成病毒核糖核蛋白（viral ribonucleoprotein，vRNP）复合物，指导病毒基因组的转录和复制。宿主因子ANP 32蛋白已被证明与vRNP相关，并且对于禽流感病毒的聚合酶活性和跨种限制是必需的。然而，ANP 32支持聚合酶活性的分子机制在很大程度上是未知的。在此，我们鉴定了KPNA 6与流感病毒的ANP 32 A/B和vRNP相关。KPNA 6的敲除和过表达均通过抑制聚合酶活性来下调流感病毒的复制，表明一定水平的KPNA 6有利于流感病毒的有效复制。此外，我们证明KPNA 6或其核输入结构域负突变的过表达抑制了ANP 32和vRNP之间的相互作用，从而降低了聚合酶活性。我们的研究结果揭示了KPNA 6在与ANP 32 A/B和vRNP相互作用以维持病毒聚合酶活性中的作用，并为进一步理解ANP 32支持流感聚合酶的机制提供了新的见解。重要性宿主因子ANP 32在支持流感病毒的聚合酶活性方面起着重要作用，但其潜在机制在很大程度上尚不清楚。在此，我们提出KPNA 6通过与vRNP和ANP 32 A/B相互作用而参与ANP 32 A/B支持流感病毒聚合酶的功能。KPNA 6-ANP 32-vRNP复合物中KPNA 6和ANP 32蛋白的适当量对于维持病毒聚合酶活性至关重要。KPNA 6可能有助于维持vRNA和ANP 32蛋白在细胞核中的稳定相互作用，并且这种功能不依赖于KPNA 6的已知输入结构域。我们的研究揭示了KNPA 6与支持病毒聚合酶的ANP 32蛋白相关的作用，并为开发抗病毒策略提供了新的视角。
Influenza A virus (IAV) RNA-dependent RNA polymerase (vPol) is a heterotrimer composed of PB2, PB1, and PA, which, together with vRNA and nucleoprotein (NP), forms viral ribonucleoprotein (vRNP) complex to direct the transcription and replication of the viral genome. Host factor ANP32 proteins have been proved to be associated with vRNP and are essential for polymerase activity and cross-species restriction of avian influenza virus. However, the molecular mechanism by which ANP32 supports polymerase activity is largely unknown. Here, we identified that KPNA6 is associated with ANP32A/B and vRNP of the influenza virus. Both knockout and overexpression of KPNA6 downregulate the replication of the influenza virus by inhibiting the polymerase activity, indicating that a certain level of KPNA6 is beneficial for efficient replication of the influenza virus. Furthermore, we demonstrate that overexpression of KPNA6 or its nuclear importing domain negative mutation inhibited the interaction between ANP32 and vRNP, thus reducing the polymerase activity. Our results revealed the role of KPNA6 in interacting with both ANP32A/B and vRNP to maintain viral polymerase activity and provided new insights for further understanding of the mechanism by which ANP32 supports influenza polymerase. IMPORTANCE Host factor ANP32 plays a fundamental role in supporting the polymerase activity of influenza viruses, but the underlying mechanism is largely unknown. Here, we propose that KPNA6 is involved in the function of ANP32A/B to support influenza virus polymerase by interacting with both vRNP and ANP32A/B. The proper amount of KPNA6 and ANP32 proteins in the KPNA6-ANP32-vRNP complex is crucial for maintaining the viral polymerase activity. The KPNA6 may contribute to maintaining stable interaction between vRNA and ANP32 proteins in the nucleus, and this function is independent of the known importing domain of KPNA6. Our research reveals a role of KNPA6 associated with ANP32 proteins that support the viral polymerase and suggests a new perspective for developing antiviral strategies.
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影响因子：
6.4
作者：
Park, Young Hyun;Chungu, Kelly;Han, Jae Yong
通讯作者：
Han, Jae Yong
影响因子：
6.7
作者：
Zhang, Haili;Li, Hongxin;Wang, Xiaojun
通讯作者：
Wang, Xiaojun
影响因子：
8.8
作者：
Domingues P;Hale BG
通讯作者：
Hale BG
DOI：
10.1038/nrmicro3367
发表时间：
2015-01
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Eisfeld AJ;Neumann G;Kawaoka Y
通讯作者：
Kawaoka Y
影响因子：
5.4
作者：
Staller，Ecco;Barclay，Wendy S.
通讯作者：
Barclay，Wendy S.