MicroRNA-376b-3p Promotes Porcine Reproductive and Respiratory Syndrome Virus Replication by Targeting Viral Restriction Factor TRIM22
MicroRNA-376b-3p Promotes Porcine Reproductive and Respiratory Syndrome Virus Replication by Targeting Viral Restriction Factor TRIM22
复制标题
MicroRNA-376b-3p 通过靶向病毒限制因子 TRIM22 促进猪繁殖与呼吸综合征病毒复制
DOI：
10.1128/jvi.01597-21
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发表时间：
2022-01-01
影响因子：
5.4
通讯作者：
Zhang, Yina
中科院分区：
文献类型：
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作者：
Chen, Jing;Zhao, Shijie;Zhang, Yina
猪繁殖与呼吸综合征病毒（Porcine reproductive and respiratory syndrome virus，PRRSV）是一种重要的经济病原体，它通过多种策略来逃避宿主的抗病毒反应，为宿主提供有利的生存条件。在本研究中，我们证明了宿主microRNA，miR-376 b-3 p，通过病毒组分nsp 4和nsp 11被PRRSV感染上调，并且miR-376 b-3 p可以直接靶向含有三重基序的22（TRIM 22），以削弱其抗PRRSV活性，从而促进PRRSV的复制。同时，我们发现TRIM 22通过与N蛋白相互作用诱导N蛋白降解而抑制PRRSV复制，进一步研究表明TRIM 22通过与LC 3相互作用诱导N蛋白的溶酶体降解而增强溶酶体途径的激活。综上所述，PRRSV通过降低TRIM 22的抗病毒作用，增加了miR-376 b-3 p的表达，并劫持了宿主miR-376 b-3 p，从而促进了PRRSV的复制。因此，我们的发现为猪繁殖与呼吸综合征病毒（Porcine reproductive and respiratory syndrome virus，PRRSV）的免疫逃逸提供了一种新的策略，有助于更好地理解PRRSV的致病机理。microRNAs（miRNAs）通过在转录后水平调节病毒或宿主基因的表达，在病毒感染过程中发挥重要作用。TRIM 22最近已被鉴定为抑制许多人类病毒（如HIV、脑心肌炎病毒（ECMV）、丙型肝炎病毒（HCV）、HBV、甲型流感病毒（IAV）和呼吸道合胞病毒（RSV））复制的关键限制因子。在这项研究中，我们发现宿主miR-376 b-3 p可以被PRRSV上调，并发挥功能削弱TRIM 22的抗PRRSV作用，以促进PRRSV复制。同时，我们发现TRIM 22通过与病毒N蛋白相互作用并通过溶酶体途径加速其降解而抑制PRRSV的复制。总的来说，这些发现揭示了PRRSV利用宿主miR-376 b-3 p逃避抗病毒反应的新机制，并为病毒-宿主相互作用的研究提供了新的见解。
Porcine reproductive and respiratory syndrome virus (PRRSV) is a major economically significant pathogen and has evolved several strategies to evade host antiviral response and provide favorable conditions for survival. In the present study, we demonstrated that a host microRNA, miR-376b-3p, was upregulated by PRRSV infection through the viral components, nsp4 and nsp11, and that miR-376b-3p can directly target tripartite motif-containing 22 (TRIM22) to impair its anti-PRRSV activity, thus facilitating the replication of PRRSV. Meanwhile, we found that TRIM22 induced degradation of the nucleocapsid protein (N) of PRRSV by interacting with N protein to inhibit PRRSV replication, and further study indicated that TRIM22 could enhance the activation of the lysosomal pathway by interacting with LC3 to induce lysosomal degradation of N protein. In conclusion, PRRSV increased miR-376b-3p expression and hijacked the host miR-376b-3p to promote PRRSV replication by impairing the antiviral effect of TRIM22. Therefore, our finding outlines a novel strategy of immune evasion exerted by PRRSV, which is helpful for better understanding the pathogenesis of PRRSV.IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) causes enormous economic losses each year in the swine industry worldwide. MicroRNAs (miRNAs) play important roles during viral infections via modulating the expression of viral or host genes at the posttranscriptional level. TRIM22 has recently been identified as a key restriction factor that inhibited the replication of a number of human viruses, such as HIV, encephalomyocarditis virus (ECMV), hepatitis C virus (HCV), HBV, influenza A virus (IAV), and respiratory syncytial virus (RSV). In this study, we showed that host miR-376b-3p could be upregulated by PRRSV and functioned to impair the anti-PRRSV role of TRIM22 to facilitate PRRSV replication. Meanwhile, we found that TRIM22 inhibited the replication of PRRSV by interacting with viral N protein and accelerating its degradation through the lysosomal pathway. Collectively, the findings reveal a novel mechanism that PRRSV used to exploit the host miR-376b-3p to evade antiviral responses and provide new insight into the study of virus-host interactions.