Rotavirus NSP1 Inhibits Type I and Type III Interferon Induction

被引：22

作者：

Iaconis, Gennaro ^{[1
,2
,5
]}

Jackson, Ben ^{[1
]}

Childs, Kay ^{[1
]}

Boyce, Mark ^{[3
]}

Goodbourn, Stephen ^{[4
]}

Blake, Neil ^{[2
]}

Iturriza-Gomara, Miren ^{[2
]}

Seago, Julian ^{[1
]}

机构：

[1] Pirbright Inst, Ash Rd, Woking GU24 0NF, Surrey, England

[2] Univ Liverpool, Inst Infect Vet & Ecol Sci, Liverpool L69 7BE, Merseyside, England

[3] Univ Oxford, Wellcome Trust Ctr Human Genet, Div Struct Biol, Oxford OX3 7BN, England

[4] St Georges Univ London, Inst Infect & Immun, London SW17 0RE, England

[5] Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge CB2 1TN, England

来源：

VIRUSES-BASEL | 2021年 / 13卷 / 04期

基金：

英国生物技术与生命科学研究理事会;

关键词：

rotavirus; type I interferon; type III interferon; NSP1; IRF-1; IRF-3; IRF-7; NF-κ B; NF-KAPPA-B; SWINE-FEVER VIRUS; ANTIVIRAL RESPONSES; REGULATORY FACTOR-3; DEGRADATION; EXPRESSION; BINDING; ACTIVATION; MECHANISM; REQUIRES;

D O I：

10.3390/v13040589

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Type I interferons (IFNs) are produced by most cells in response to virus infection and stimulate a program of anti-viral gene expression in neighboring cells to suppress virus replication. Type III IFNs have similar properties, however their effects are limited to epithelial cells at mucosal surfaces due to restricted expression of the type III IFN receptor. Rotavirus (RV) replicates in intestinal epithelial cells that respond predominantly to type III IFNs, and it has been shown that type III rather than type I IFNs are important for controlling RV infections in vivo. The RV NSP1 protein antagonizes the host type I IFN response by targeting IRF-3, IRF-5, IRF-7, or beta-TrCP for proteasome-mediated degradation in a strain-specific manner. Here we provide the first demonstration that NSP1 proteins from several human and animal RV strains antagonize type III as well as type I IFN induction. We also show that NSP1 is a potent inhibitor of IRF-1, a previously undescribed property of NSP1 which is conserved among human and animal RVs. Interestingly, all NSP1 proteins were substantially more effective inhibitors of IRF-1 than either IRF-3 or IRF-7 which has significance for evasion of basal anti-viral immunity and type III IFN induction in the intestinal epithelium.

引用

页数：17

共 53 条

[1] The Rotavirus Interferon Antagonist NSP1: Many Targets, Many Questions [J].