Equine Viperin Restricts Equine Infectious Anemia Virus Replication by Inhibiting the Production and/or Release of Viral Gag, Env, and Receptor via Distortion of the Endoplasmic Reticulum

文献类型： 外文期刊

第一作者： Tang, Yan-Dong

作者： Tang, Yan-Dong;Li, Cheng-Yao;Tang, Yan-Dong;Na, Lei;Zhu, Chun-Hui;Shen, Nan;Yang, Fei;Fu, Li-Hua;Wang, Jia-Yi;Lin, Yue-Zhi;Wang, Xue-Feng;Wang, Xiaojun;Zhou, Jian-Hua;Zhou, Jian-Hua;Fu, Xian-Qiu;Wang, Yu-Hong

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期刊名称：JOURNAL OF VIROLOGY （ 影响因子：5.103； 五年影响因子：5.078 ）

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收录情况： SCI

摘要： Viperin is an endoplasmic reticulum ( ER)-associated multifunctional protein that regulates virus replication and possesses broad antiviral activity. In many cases, viperin interferes with the trafficking and budding of viral structural proteins by distorting the membrane transportation system. The lentivirus equine infectious anemia virus (EIAV) has been studied extensively. In this study, we examined the restrictive effect of equine viperin (eViperin) on EIAV replication and investigated the possible molecular basis of this restriction to obtain insights into the effect of this cellular factor on retroviruses. We demonstrated that EIAV infection of primary equine monocyte-derived macrophages (eMDMs) upregulated the expression of eViperin. The overexpression of eViperin significantly inhibited the replication of EIAV in eMDMs, and knockdown of eViperin transcription enhanced the replication of EIAV in eMDMs by approximately 45.8%. Further experiments indicated that eViperin restricts EIAV at multiple steps of viral replication. The overexpression of eViperin inhibited EIAV Gag release. Both the alpha-helix domain and radical S-adenosylmethionine (SAM) domain were required for this activity. However, the essential motifs in SAM were different from those reported for the inhibition of HIV-1 Gag by human viperin. Furthermore, eViperin disrupted the synthesis of both EIAV Env and receptor, which consequently inhibited viral production and entry, respectively, and this disruption was dependent on the eViperin alpha-helix domain. Using immunofluorescence assays and electron microscopy, we demonstrated that the alpha-helix domain is responsible for the distortion of the endoplasmic reticulum (ER). Finally, EIAV did not exhibit counteracting eViperin at the protein level. IMPORTANCE In previous studies, viperin was indicated as restricting virus replications primarily by the inhibition of virus budding. Here, we show that viperin may have multiple antiviral mechanisms, including the reduction of EIAV Gag budding and Env expression, and these activities are dependent on different viperin domains. We especially demonstrate that the overexpression of viperin inhibits EIAV entry by decreasing the level of virus receptor. Therefore, viperin restriction of viruses is determined largely by the dependence of virus on the cellular membrane transportation system.

分类号： Q934.2

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