Hemoglobin Subunit Beta Interacts with the Capsid Protein and Antagonizes the Growth of Classical Swine Fever Virus
Hemoglobin Subunit Beta Interacts with the Capsid Protein and Antagonizes the Growth of Classical Swine Fever Virus
复制标题
血红蛋白亚基 Beta 与衣壳蛋白相互作用并拮抗猪瘟病毒的生长
DOI：
10.1128/jvi.03130-12
复制
发表时间：
2013-05-01
影响因子：
5.4
通讯作者：
Qiu, Hua-Ji
中科院分区：
文献类型：
--
作者：
Li, Dan;Dong, Hong;Qiu, Hua-Ji
摘要黄病毒家族成员的衣壳(C)蛋白参与核衣壳的形成和病毒粒子的组装。然而，C蛋白相互作用伙伴对鼠疫病毒感染结局的影响尚不清楚。在本研究中，通过谷胱甘肽S转移酶下拉和随后对猪瘟病毒的许可细胞PK-15进行的质谱分析，确定Hb亚基是一种C蛋白结合蛋白。免疫共沉淀和共聚焦显微镜证实，Hb与细胞质中的C蛋白相互作用并共定位。用小干扰RNA沉默Hb可促进CSFV的生长和复制，而过表达Hb则抑制CSFV的复制和生长。有趣的是，Hb被发现与维甲酸诱导基因I相互作用并增加其表达，导致I型干扰素(干扰素)的产生增加。然而，当RIG-I途径被阻断时，Hb无法抑制CSFV的生长。总体而言，我们的结果表明，细胞内的Hb通过触发干扰素信号来拮抗CSFV的生长和复制，并可能代表一种新的抗病毒限制因子。这项研究首次报道了Hb在天然免疫中的新作用。
ABSTRACT The capsid (C) protein of the Flaviviridae family members is involved in nucleocapsid formation and virion assembly. However, the influence of C protein-interacting partners on the outcome of pestivirus infections is poorly defined. In this study, hemoglobin subunit beta (HB) was identified as a C protein-binding protein by glutathione S-transferase pulldown and subsequent mass spectrometry analysis of PK-15 cells, which are permissive cells for classical swine fever virus (CSFV). Coimmunoprecipitation and confocal microscopy confirmed that HB interacts and colocalizes with the C protein in the cytoplasm. Silencing of HB with small interfering RNAs promoted CSFV growth and replication, whereas overexpression of HB suppressed CSFV replication and growth. Interestingly, HB was found to interact with retinoic acid-inducible gene I and increase its expression, resulting in increased production of type I interferon (IFN). However, HB was unable to suppress CSFV growth when the RIG-I pathway was blocked. Overall, our results suggest that cellular HB antagonizes CSFV growth and replication by triggering IFN signaling, and might represent a novel antiviral restriction factor. This study reports for the first time the novel role of HB in innate immunity.