流感病毒的NS1蛋白是一个关键致病因子，它通过多种机制、包括双链RNA的结合和隔离来拮抗宿主的抗病毒反应。
在新一期Nature中，美国贝勒医学院的研究人员利用在2004年越南禽流感爆发期间分离出的一个恶性H5N1禽流感病毒毒株，确定了全长NS1蛋白的结构。该分子的RNA结合区域与非H5N1毒株的RNA结合区域相比有微妙的差别，而效应子区域则有较大改变。这两个区域以某种方式发生相互作用，形成小管，后者可能会隔离双链RNA，从而让病毒躲过宿主的先天免疫反应。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 456, 985-988 (18 December 2008) | doi:10.1038/nature07444
X-ray structure of NS1 from a highly pathogenic H5N1 influenza virus
Zachary A. Bornholdt1 & B. V. Venkataram Prasad1,2
1 Department of Molecular Virology and Microbiology,
2 Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
The recent emergence of highly pathogenic avian (H5N1) influenza viruses, their epizootic and panzootic nature, and their association with lethal human infections have raised significant global health concerns1, 2. Several studies have underlined the importance of non-structural protein NS1 in the increased pathogenicity and virulence of these strains3, 4. NS1, which consists of two domains—a double-stranded RNA (dsRNA) binding domain5, 6 and the effector domain7, separated through a linker—is an antagonist of antiviral type-I interferon response in the host8, 9. Here we report the X-ray structure of the full-length NS1 from an H5N1 strain (A/Vietnam/1203/2004) that was associated with 60% of human deaths in an outbreak in Vietnam1, 2. Compared to the individually determined structures of the RNA binding domain and the effector domain from non-H5N1 strains, the RNA binding domain within H5N1 NS1 exhibits modest structural changes, while the H5N1 effector domain shows significant alteration, particularly in the dimeric interface. Although both domains in the full-length NS1 individually participate in dimeric interactions, an unexpected finding is that these interactions result in the formation of a chain of NS1 molecules instead of distinct dimeric units. Three such chains in the crystal interact with one another extensively to form a tubular organization of similar dimensions to that observed in the cryo-electron microscopy images of NS1 in the presence of dsRNA. The tubular oligomeric organization of NS1, in which residues implicated in dsRNA binding face a 20-?-wide central tunnel, provides a plausible mechanism for how NS1 sequesters varying lengths of dsRNA, to counter cellular antiviral dsRNA response pathways, while simultaneously interacting with other cellular ligands during an infection.
