BINDING OF THE INFLUENZA-VIRUS NS1 PROTEIN TO DOUBLE-STRANDED-RNA INHIBITS THE ACTIVATION OF THE PROTEIN-KINASE THAT PHOSPHORYLATES THE ELF-2 TRANSLATION INITIATION-FACTOR

被引：336

作者：

LU, Y

WAMBACH, M

KATZE, MG

KRUG, RM

机构：

[1] RUTGERS STATE UNIV,DEPT MOLEC BIOL & BIOCHEM,PISCATAWAY,NJ 08855

[2] UNIV WASHINGTON,SCH MED,DEPT MICROBIOL,SEATTLE,WA 98195

来源：

VIROLOGY | 1995年 / 214卷 / 01期

关键词：

D O I：

10.1006/viro.1995.9937

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

The NS1 protein of influenza A virus binds not only to poly(A) and a stem-bulge region in U6 small nuclear RNA (snRNA), but also to double-stranded (ds) RNA. Binding assays with NS1 protein mutants established that the previously identified RNA-binding domain of the NS1 protein is required for binding to ds RNA as well as for binding to poly(A) and U6 snRNA. In addition, dsRNA competed with U6 snRNA for binding to the NS1 protein, consistent with both RNAs sharing the same binding site on the protein. As a consequence of its binding to dsRNA, the NS1 protein blocks the activation of the dsRNA-activated protein kinase (PKR) in vitro. This kinase phosphorylates the cu subunit of eukaryotic translation initiation factor 2 (elF-2 alpha), leading to a decrease in the rate of initiation of translation. Assays using purified PKR and purified elF2 demonstrated that the NS1 protein blocks the dsRNA activation of PKR, and experiments using reticulocyte extracts showed that the NS1 protein blocks the inhibition of translation caused by dsRNA activation of PKR. The implications of these results for control mechanisms occurring in influenza virus-infected cells are discussed. (C) 1995 Academic Press, Inc.

引用

页码：222 / 228

页数：7

共 35 条

[21]

Lee T.G., Tomia J., Hovanessian A.G., Katze M.G., Characterization and regulation of the 58, 000-dalton cellular inhibitor of the interferon-induced, dsRNA activated protein kinase, J. Biol. Chem, 267, pp. 14238-14243, (1992)

[22]

Lloyd R.M., Shatkin A.J., Translational stimulation by reovirus polypeptide s3: Substitution for VAI RNA and inhibition of phosphorylation of the a subunit of eukaryotic initiation factor 2, J. Virol, 66, pp. 6878-6884, (1992)

[23]

Lodish H.F., Model for the regulation of mRNA translation applied to hemoglobin synthesis, Nature (London), 251, pp. 385-388, (1974)

[24]

Lodish H.F., Translational control of protein synthesis, Annu. Rev. Biochem, 45, pp. 39-72, (1976)

[25]

Lu Y., Qian X.-Y., Krug R.M., The influenza virus NS1 protein: A novel inhibitor of pre-mRNA splicing, Genes Dev, 8, pp. 1817-1828, (1994)

[26]

Luna S., Fortes P., Beloso A., Ortin J., Influenza virus NS1 protein enhances the rate of translation initiation of viral mRNAs, J. Virol, 69, pp. 2427-2433, (1995)

[27]

Mathews M.B., Viral evasion of cellular defense mechanisms: Regulation of the protein kinase DAI by RNA effectors, Semin. Virol, 4, pp. 247-257, (1993)

[28]

Merrick W., Mechanism and regulation of eukaryotic protein synthesis, Microbiol. Rev, 56, pp. 291-315, (1992)

[29]

Qian X.-Y., Alonso-Caplen F., Krug R.M., Two functional domains of the influenza virus NS1 protein are required for regulation of nuclear export of mRNA, J. Virol, 68, pp. 2433-2441, (1994)

[30]

Qiu Y., Krug R.M., The influenza virus NS1 protein is a poly(A)-binding protein that inhibits nuclear export of mRNAs containing poly(A), J. Virol, 68, pp. 2425-2432, (1994)

← 1 2 3 4 →