Broad Impact of Exchange Protein Directly Activated by cAMP 2 (EPAC2) on Respiratory Viral Infections.
Broad Impact of Exchange Protein Directly Activated by cAMP 2 (EPAC2) on Respiratory Viral Infections.
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DOI：
10.3390/v13061179
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发表时间：
2021-06-21
期刊：
影响因子：
--
通讯作者：
Bao X
中科院分区：
文献类型：
--
作者：
Choi EJ;Wu W;Cong X;Zhang K;Luo J;Ye S;Wang P;Suresh A;Ullah UM;Zhou J;Bao X
与蛋白激酶A（PKA）相比，最近发现的cAMP直接激活的交换蛋白（EPAC）是一个相当新的cAMP效应子家族。发现后不久，EPAC就在许多疾病中显示出其重要性，包括其在传染病中的新兴作用。在最近的一项研究中，我们证明了EPAC，而不是PKA，是一个有前途的治疗靶点，以调节呼吸道合胞病毒（RSV）的复制及其相关的炎症。在哺乳动物中，有两种EPAC亚型-EPAC 1和EPAC 2。与其他病毒不同，包括中东呼吸综合征冠状病毒（MERS-CoV）和埃博拉病毒，它们使用EPAC 1来调节病毒复制，RSV使用EPAC 2来控制其复制和相关的细胞因子/趋化因子反应。为了确定EPAC 2蛋白是否对其他呼吸道病毒感染具有广泛的影响，我们使用EPAC 2特异性抑制剂MAY 0132来检查EPAC 2在人类偏肺病毒（HMPV）和腺病毒（AdV）感染中的功能。HMPV是属于肺病毒科的负义单链RNA病毒，其还包括RSV，而AdV是双链DNA病毒。还包括用EPAC 1特异性抑制剂处理以研究EPAC 1对这两种病毒的影响。我们发现HMPV、AdV和RSV的复制以及病毒诱导的免疫介质被MAY 0132显著损害，而EPAC 1特异性抑制剂CE 3F 4不影响或轻微影响，表明EPAC 2可以作为控制这些病毒的新的常见治疗靶点，所有这些病毒都没有有效的治疗和预防策略。
The recently discovered exchange protein directly activated by cAMP (EPAC), compared with protein kinase A (PKA), is a fairly new family of cAMP effectors. Soon after the discovery, EPAC has shown its significance in many diseases including its emerging role in infectious diseases. In a recent study, we demonstrated that EPAC, but not PKA, is a promising therapeutic target to regulate respiratory syncytial virus (RSV) replication and its associated inflammation. In mammals, there are two isoforms of EPAC—EPAC1 and EPAC2. Unlike other viruses, including Middle East respiratory syndrome coronavirus (MERS-CoV) and Ebola virus, which use EPAC1 to regulate viral replication, RSV uses EPAC2 to control its replication and associated cytokine/chemokine responses. To determine whether EPAC2 protein has a broad impact on other respiratory viral infections, we used an EPAC2-specific inhibitor, MAY0132, to examine the functions of EPAC2 in human metapneumovirus (HMPV) and adenovirus (AdV) infections. HMPV is a negative-sense single-stranded RNA virus belonging to the family Pneumoviridae, which also includes RSV, while AdV is a double-stranded DNA virus. Treatment with an EPAC1-specific inhibitor was also included to investigate the impact of EPAC1 on these two viruses. We found that the replication of HMPV, AdV, and RSV and the viral-induced immune mediators are significantly impaired by MAY0132, while an EPAC1-specific inhibitor, CE3F4, does not impact or slightly impacts, demonstrating that EPAC2 could serve as a novel common therapeutic target to control these viruses, all of which do not have effective treatment and prevention strategies.
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影响因子：
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作者：
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期刊：
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发表时间：
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