Heaton Brook E, Kennedy Edward M, Dumm Rebekah E, Harding Alfred T, Sacco Matthew T, Sachs David, Heaton Nicholas S
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Cell Rep. 2017 Aug 15;20(7):1503-1512. doi: 10.1016/j.celrep.2017.07.060.
Influenza A virus (IAV) is a pathogen that poses significant risks to human health. It is therefore critical to develop strategies to prevent influenza disease. Many loss-of-function screens have been performed to identify the host proteins required for viral infection. However, there has been no systematic screen to identify the host factors that, when overexpressed, are sufficient to prevent infection. In this study, we used CRISPR/dCas9 activation technology to perform a genome-wide overexpression screen to identify IAV restriction factors. The major hit from our screen, B4GALNT2, showed inhibitory activity against influenza viruses with an α2,3-linked sialic acid receptor preference. B4GALNT2 overexpression prevented the infection of every avian influenza virus strain tested, including the H5, H9, and H7 subtypes, which have previously caused disease in humans. Thus, we have used CRISPR/dCas9 activation technology to identify a factor that can abolish infection by avian influenza viruses.
甲型流感病毒（IAV）是一种对人类健康构成重大风险的病原体。因此，制定预防流感疾病的策略至关重要。已经进行了许多功能丧失筛选，以确定病毒感染所需的宿主蛋白。然而，尚未有系统的筛选来确定那些过表达时足以预防感染的宿主因子。在本研究中，我们使用CRISPR/dCas9激活技术进行全基因组过表达筛选，以鉴定IAV限制因子。我们筛选出的主要命中基因B4GALNT2，对偏好α2,3连接唾液酸受体的流感病毒具有抑制活性。B4GALNT2的过表达可预防所测试的每一种禽流感病毒株的感染，包括先前已导致人类发病的H5、H9和H7亚型。因此，我们利用CRISPR/dCas9激活技术鉴定出了一种可消除禽流感病毒感染的因子。
