IFITM3 inhibits influenza A virus infection by preventing cytosolic entry.
IFITM3 inhibits influenza A virus infection by preventing cytosolic entry.
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DOI：
10.1371/journal.ppat.1002337
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发表时间：
2011-10
期刊：
影响因子：
6.7
通讯作者：
Brass AL
中科院分区：
文献类型：
--
作者：
Feeley EM;Sims JS;John SP;Chin CR;Pertel T;Chen LM;Gaiha GD;Ryan BJ;Donis RO;Elledge SJ;Brass AL
为了复制，病毒必须获得宿主细胞的资源。干扰素（IFN）调节大量干扰素效应基因（IEGs）的作用，以防止病毒复制。干扰素诱导跨膜蛋白家族成员IFITM 1、2和3是体外抑制甲型流感病毒、登革热病毒和西尼罗病毒复制所需的IEGs。在这里，我们报告说，干扰素防止出现的病毒基因组从内体途径，IFITM3是必要的和足够的这一功能。值得注意的是，病毒假颗粒被IFN抑制将其内容物转移到宿主细胞胞质溶胶中，并且IFITM3对于该作用是必需的并且是足够的。我们进一步证明，IFN扩展Rab7和LAMP 1的结构，IFITM3过表达是足够的这种表型。此外，IFITM3部分存在于晚期内体和溶酶体结构中，将其置于入侵病毒的路径中。总的来说，我们的数据与预测一致，即在晚期内体或溶酶体中融合的病毒容易受到IFITM3的作用，而在细胞表面或早期内体中进入的病毒可能会避免抑制。多种病毒通过晚期内吞途径进入宿主细胞，并且这些入侵者中的许多被IFN减弱。因此，这些发现可能对内在免疫系统中和各种威胁具有重要意义。流行性感冒对世界卫生造成巨大损失。因此，研究确定新的抗流感病毒策略将是有益的。我们的每个细胞都含有抗病毒因子，可以抑制感染。这种抗病毒程序的很大一部分是由干扰素家族的信号分子调节的。在这里，我们试图更好地了解这些抗病毒因子之一，IFITM3，如何有助于基线，以及干扰素诱导，拮抗甲型流感病毒感染。我们发现干扰素通过阻断病毒与细胞膜的融合来阻止甲型流感病毒进入我们的细胞。此外，我们了解到干扰素的这种抗病毒作用需要IFITM3，并且高水平的IFITM3单独可以产生类似的病毒抑制作用。总之，这些结果提高了我们对IFITM3如何在感染的早期阶段保护我们免受病毒入侵的理解。
To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats. Influenza epidemics exact a great toll on world health. Thus research to identify new anti-influenza virus strategies would be useful. Each of our cells contains antiviral factors that work to inhibit infection. A large component of this antiviral program is regulated by the interferon family of signaling molecules. Here, we seek to better understand how one of these antiviral factors, IFITM3, contributes to both baseline, as well as interferon-induced, antagonism of influenza A viral infection. We found that interferon prevents influenza A virus from entering our cells by blocking the virus' fusion with the cellular membrane. Furthermore, we learned that IFITM3 is required for this antiviral action of interferon, and that high levels of IFITM3 alone can produce a similar viral inhibition. Together, these results improve our understanding of how IFITM3 serves to defend us against viral invasion at a very early stage of infection.
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跨膜蛋白的脆弱性干扰素诱导基因家族与小鼠的生殖细胞规范有关。
影响因子：
--
作者：
Lange, U C;Saitou, M;Western, P S;Barton, S C;Surani, M A
通讯作者：
Surani, M A
影响因子：
5.4
作者：
Bui, M;Wills, EG;Whittaker, GR
通讯作者：
Whittaker, GR
影响因子：
4.8
作者：
Lawe, DC;Chawla, A;Corvera, S
通讯作者：
Corvera, S
影响因子：
3.7
作者：
Bernard E;Solignat M;Gay B;Chazal N;Higgs S;Devaux C;Briant L
通讯作者：
Briant L
影响因子：
120.7
作者：
Bridges, CB;Thompson, WW;Fukuda, K
通讯作者：
Fukuda, K