Species-Specific Antagonism of Host ISGylation by the Influenza B Virus NS1 Protein
Species-Specific Antagonism of Host ISGylation by the Influenza B Virus NS1 Protein
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DOI：
10.1128/jvi.02395-09
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发表时间：
2010-05-01
影响因子：
5.4
通讯作者：
Garcia-Sastre, Adolfo
中科院分区：
文献类型：
--
作者：
Versteeg, Gijs A.;Hale, Benjamin G.;Garcia-Sastre, Adolfo
干扰素刺激的泛素样修饰物ISG15的表达和结合限制了几种病毒的复制。在这里，我们建立了完整的E1激活、E2结合和E3连接酶依赖的表达系统，用于检测人和小鼠的ISG化。我们证实人的HerC5而不是人的HerC6具有ISG15 E3连接酶活性，并鉴定小鼠HerC6为真正的ISG15 E3连接酶。此外，我们证明了B型流感病毒NS1蛋白有效地拮抗人而不是小鼠的ISG化，这一特性依赖于B/NS1结合人的N端结构域而不是小鼠的ISG15。使用人/鼠嵌合的ISG15结构，我们证明了B/NS1：ISG15的相互作用是必要的，也是充分的，无论使用何种连接机制，都可以抑制ISG化。不能阻止某些物种的ISG化可能有助于限制B型流感病毒的宿主范围。
Interferon-stimulated expression and conjugation of the ubiquitin-like modifier ISG15 restricts replication of several viruses. Here, we established complete E1-activating, E2-conjugating, and E3 ligase-dependent expression systems for assaying both human and mouse ISGylation. We confirm that human HerC5, but not human HerC6, has ISG15 E3 ligase activity and identify mouse HerC6 as a bona fide ISG15 E3 ligase. Furthermore, we demonstrate that influenza B virus NS1 protein potently antagonizes human but not mouse ISGylation, a property dependent on B/NS1 binding the N-terminal domain of human but not mouse ISG15. Using chimeric human/mouse ISG15 constructs, we show that the B/NS1:ISG15 interaction is both necessary and sufficient to inhibit ISGylation regardless of the ligation machinery used. Inability to block ISGylation in certain species may contribute to limiting influenza B virus host range.