A dive into the complexity of type I interferon antiviral functions

被引:5
|
作者
Touzot, Maxime [2 ,3 ]
Soumelis, Vassili [2 ,3 ]
Asselah, Tarik [1 ,4 ,5 ]
机构
[1] Hop Beaujon, CRB3, INSERM, U773,Serv Hepatol, F-92110 Clichy, France
[2] INSERM, U932, Paris, France
[3] Inst Curie, Clin Immunol Lab, Paris, France
[4] Ctr Rech Bichat Beaujon CRB3 Paris, INSERM, U773, Paris, France
[5] Univ Paris Diderot, Paris, France
关键词
COMBINATION; EXPRESSION;
D O I
10.1016/j.jhep.2011.07.009
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
The type I interferon response protects cells against invading viral pathogens. The cellular factors that mediate this defense are the products of interferon-stimulated genes (ISGs). Although hundreds of ISGs have been identified since their discovery more than 25 years ago, only a few have been characterized with respect to antiviral activity. For most ISG products, little is known about their antiviral potential, their target specificity, and their mechanisms of action. Using an overexpression screening approach, here we show that different viruses are targeted by unique sets of ISGs. We find that each viral species is susceptible to multiple antiviral genes, which together encompass a range of inhibitory activities. To conduct the screen, more than 380 human ISGs were tested for their ability to inhibit the replication of several important human and animal viruses, including hepatitis C virus, yellow fever virus, West Nile virus, chikungunya virus, Venezuelan equine encephalitis virus, and human immunodeficiency virus type-1. Broadly acting effectors included IRF1, C6orf150 (also known as MB21D1), HPSE, RIG-I (also known as DDX58), MDA5 (also known as IFIH1), and IFITM3, whereas more targeted antiviral specificity was observed with DDX60, IFI44L, IFI6, IFITM2, MAP3K14, MOV10, NAMPT (also known as PBEF1), OASL, RTP4, TREX1, and UNC84B (also known as SUN2). Combined expression of pairs of ISGs showed additive antiviral effects similar to those of moderate type I interferon doses. Mechanistic studies uncovered a common theme of translational inhibition for numerous effectors. Several ISGs, including ADAR, FAM46C, LY6E, and MCOLN2, enhanced the replication of certain viruses, highlighting another layer of complexity in the highly pleiotropic type I interferon system. (C) 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:726 / 728
页数:3
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