Influenza virus-host interactome screen as a platform for antiviral drug development.
Influenza virus-host interactome screen as a platform for antiviral drug development.
复制标题
DOI：
10.1016/j.chom.2014.11.002
复制
发表时间：
2014-12-10
影响因子：
30.3
通讯作者：
Kawaoka Y
中科院分区：
文献类型：
--
作者：
Watanabe T;Kawakami E;Shoemaker JE;Lopes TJ;Matsuoka Y;Tomita Y;Kozuka-Hata H;Gorai T;Kuwahara T;Takeda E;Nagata A;Takano R;Kiso M;Yamashita M;Sakai-Tagawa Y;Katsura H;Nonaka N;Fujii H;Fujii K;Sugita Y;Noda T;Goto H;Fukuyama S;Watanabe S;Neumann G;Oyama M;Kitano H;Kawaoka Y
病毒复制所需的宿主因子是理想的药物靶点，因为它们在药物介导的选择压力下不太可能比病毒蛋白质突变。虽然全基因组筛选已经确定了参与流感病毒复制的宿主蛋白，但对这些因素如何影响流感的机制了解有限，阻碍了潜在的药物开发。我们进行了系统的分析，以确定和验证与流感病毒蛋白相关并影响病毒复制的宿主因素。在鉴定了与特定病毒蛋白共免疫沉淀的一千多种宿主因子后，我们基于受宿主因子下调影响的病毒生命周期阶段生成了病毒-宿主蛋白相互作用的网络。使用抑制这些宿主因子的化合物，我们验证了几种蛋白质，特别是高尔基体特异性布雷菲德菌素A抗性鸟嘌呤核苷酸交换因子（GBF 1）和JAK 1，作为潜在的抗病毒药物靶点。因此，病毒-宿主相互作用组筛选是鉴定靶向宿主因子和指导抗病毒药物开发的有力策略。
Host factors required for viral replication are ideal drug targets because they are less likely than viral proteins to mutate under drug-mediated selective pressure. Although genome-wide screens have identified host proteins involved in influenza virus replication, limited mechanistic understanding of how these factors affect influenza has hindered potential drug development. We conducted a systematic analysis to identify and validate host factors that associate with influenza virus proteins and affect viral replication. After identifying over one thousand host factors that co-immunoprecipitate with specific viral proteins, we generated a network of virus-host protein interactions based on the stage of the viral lifecycle affected upon host factor down-regulation. Using compounds that inhibit these host factors, we validated several proteins, notably Golgi-specific brefeldin A resistant guanine nucleotide exchange factor (GBF1) and JAK1, as potential antiviral drug targets. Thus, virus-host interactome screens are powerful strategies to identify targetable host factors and guide antiviral drug development.
登录
查看更多内容
人类感染新型禽源甲型流感 (H7N9) 病毒。
影响因子：
158.5
作者：
Gao, Rongbao;Cao, Bin;Shu, Yuelong
通讯作者：
Shu, Yuelong
DOI：
10.1098/rstb.2001.1007
发表时间：
2001-12-29
影响因子：
6.3
作者：
Hayden, FG
通讯作者：
Hayden, FG
影响因子：
64.5
作者：
Marsh M;Helenius A
通讯作者：
Helenius A
影响因子：
5.4
作者：
Li, Zejun;Watanabe, Tokiko;Kawaoka, Yoshihiro
通讯作者：
Kawaoka, Yoshihiro
影响因子：
5.4
作者：
Elton, D;Simpson-Holley, M;Digard, P
通讯作者：
Digard, P