Induction of type I interferon by adenovirus-encoded small RNAs

被引：53

作者：

Yamaguchi, Tomoko ^{[1
,2
]}

Kawabata, Kenji ^{[1
,2
]}

Kouyama, Emi ^{[2
]}

Ishii, Ken J. ^{[3
,4
]}

Katayama, Kazufumi ^{[1
]}

Suzuki, Takayuki ^{[1
,2
]}

Kurachi, Shinnosuke ^{[1
,2
]}

Sakurai, Fuminori ^{[1
]}

Akira, Shizuo ^{[5
]}

Mizuguchi, Hiroyuki ^{[1
,2
]}

机构：

[1] Osaka Univ, Grad Sch Pharmaceut Sci, Suita, Osaka 5650871, Japan

[2] Natl Inst Biomed Innovat, Lab Stem Cell Regulat, Osaka 5670085, Japan

[3] Natl Inst Biomed Innovat, Lab Adjuvant Innovat, Osaka 5670085, Japan

[4] Osaka Univ, Lab Vaccine Sci, Suita, Osaka 5650871, Japan

[5] Osaka Univ, Lab Host Def, World Premier Int Immunol Frontier Res Ctr, Suita, Osaka 5650871, Japan

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 40期

关键词：

innate immune response; IFN-beta promoter stimulator-1; virus-associated RNA; INNATE IMMUNE-RESPONSE; VIRUS-ASSOCIATED RNA; RIG-I; ANTIVIRAL RESPONSES; HETEROLOGOUS PEPTIDES; DENDRITIC CELLS; DAI DLM-1/ZBP1; PROTEIN-KINASE; FIBER KNOB; VECTORS;

D O I：

10.1073/pnas.1009823107

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Transduction with replication-incompetent recombinant adenovirus (Ad) vectors results in a rapid activation of innate immune responses, such as inflammatory cytokine production and subsequent tissue damage. The precise mechanisms of the innate immune responses induced by Ad vectors remain to be clarified. Possible components of Ad vectors that activate innate immune responses are the capsid protein, the viral genome (DNA), and viral transcripts. In the present study, we demonstrate that virus-associated RNAs (VA-RNAs), which are small RNAs transcribed by RNA polymerase III, induce the production of type I IFN (IFN-alpha and IFN-beta), but they do not induce the production of inflammatory cytokines (IL-6 and IL-12), in mouse embryonic fibroblasts (MEFs) and granulocyte-macrophage colony-stimulating factor-generated bone marrow-derived dendritic cells (GM-DCs). We also show that IFN-beta promoter stimulator-1 is involved in VA-RNA-dependent IFN-beta production in MEFs and is partially involved in type I IFN production in GM-DCs. This study provides important insight into the mechanisms of Ad vector-triggered innate immune responses, which may lead to more advanced and rational Ad vector designs for gene therapies and vaccine applications.

引用

页码：17286 / 17291

页数：6

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