RNA- and Virus-Independent Inhibition of Antiviral Signaling by RNA Helicase LGP2

Journal of Virology - Tập 80 Số 24 - Trang 12332-12342 - 2006
Akihiko Komuro1,2, Curt M. Horvath1,2
1Department of Medicine and Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208
2Department of Medicine, Evanston Northwestern Healthcare, Evanston, Illinois 60208

Tóm tắt

ABSTRACT Antiviral innate immune responses can be triggered by accumulation of intracellular nucleic acids resulting from virus infections. Double-stranded RNA (dsRNA) can be detected by the cytoplasmic RNA helicase proteins RIG-I and MDA5, two proteins that share sequence similarities within a caspase recruitment domain (CARD) and a DExD/H box RNA helicase domain. These proteins are considered dsRNA sensors and are thought to transmit the signal to the mitochondrial adapter, IPS-1 (also known as MAVS, VISA, or CARDIF) via CARD interactions. IPS-1 coordinates the activity of protein kinases that activate transcription factors needed to induce beta interferon (IFN-β) gene transcription. Another helicase protein, LGP2, lacks the CARD region and does not activate IFN-β gene expression. LGP2 mRNA is induced by interferon, dsRNA treatments, or Sendai virus infection and acts as a feedback inhibitor for antiviral signaling. Results indicate that LGP2 can inhibit antiviral signaling independently of dsRNA or virus infection intermediates by engaging in a protein complex with IPS-1. Experiments suggest that LGP2 can compete with the kinase IKKi (also known as IKKε) for a common interaction site on IPS-1. These results provide the first demonstration of protein interaction as an element of negative-feedback regulation of intracellular antiviral signaling by LGP2.

Từ khóa


Tài liệu tham khảo

10.1016/j.cell.2006.02.015

10.1073/pnas.0407639101

10.1038/ni921

Gresser, I., M. Aguet, L. Morel-Maroger, D. Woodrow, F. Puvion-Dutilleul, J. C. Guillon, and C. Maury. 1981. Electrophoretically pure mouse interferon inhibits growth, induces liver and kidney lesions, and kills suckling mice. Am. J. Pathol.102:396-402.

10.1038/258076a0

10.1084/jem.20040520

Horvath, C. M. 2004. The Jak-STAT pathway stimulated by interferon alpha or interferon beta. Sci. STKE2004:tr10.

10.1111/j.1432-1033.2004.04425.x

10.1146/annurev.biochem.74.082803.133347

10.1038/ni1112

Kato, H., S. Sato, M. Yoneyama, M. Yamamoto, S. Uematsu, K. Matsui, T. Tsujimura, K. Takeda, T. Fujita, O. Takeuchi, and S. Akira. 2005. Cell type-specific involvement of RIG-I in antiviral response. Immunity175:10968-10977.

10.1038/nature04734

10.1038/ni1303

10.1038/ni1243

10.1189/jlb.0703321

10.1074/jbc.M305597200

10.1016/S0952-7915(02)00354-0

10.1128/JVI.02495-05

10.1016/j.it.2005.06.004

10.1073/pnas.2237236100

10.1016/S0092-8674(00)80412-2

10.1038/nature04193

10.1084/jem.20040528

10.4049/jimmunol.175.8.5260

10.1016/j.cell.2005.08.012

10.1126/science.1081315

10.1128/JVI.79.5.2689-2699.2005

10.1016/S1097-2765(00)80051-9

10.1016/j.molcel.2005.08.014

10.4049/jimmunol.175.5.2851

10.1038/ni1087

Thông tin
Thông tin xuất bản

Journal of Virology

Tập 80 Số 24

12332-12342

Thông tin tác giả