Nuclear factor 90 mediates activation of the cellular antiviral expression cascade
| Autor: | David Schuster, Yi-Wen Chen, Carl C. Baker, Aliyah Spruill, Ajit Kumar, Irina Krasnoselskaya-Riz, Dietrich A. Stephan, Theresa Teslovich |
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| Rok vydání: | 2002 |
| Předmět: |
Immunology
Molecular Sequence Data HIV Infections Biology Interferon Virology Gene expression medicine Tumor Cells Cultured Humans Amino Acid Sequence RNA Messenger Nuclear Factor 90 Proteins Promoter Regions Genetic Gene DNA Primers Oligonucleotide Array Sequence Analysis Immunity Cellular Innate immune system Base Sequence NFATC Transcription Factors Sequence Homology Amino Acid Reverse Transcriptase Polymerase Chain Reaction Nuclear Proteins Cell biology DNA-Binding Proteins RNA silencing Infectious Diseases Viral replication Gene Expression Regulation Cell culture Interferons Signal transduction medicine.drug Transcription Factors |
| Zdroj: | AIDS research and human retroviruses. 18(8) |
| ISSN: | 0889-2229 |
| Popis: | Viral infection triggers a cascade of interferon response genes, but the mechanisms that prime such innate antiviral defenses are poorly understood. Among candidate cellular mediators of the antiviral response are the double-stranded RNA (dsRNA)-binding proteins. Here we show that a C-terminal variant of the ubiquitous dsRNA-binding protein, nuclear factor 90 (NF90ctv), can activate the interferon response genes in the absence of viral infection. NF90ctv-expressing cells were infected with the syncytium-inducing HIV-1 strain NL4-3 and were shown to inhibit viral replication. To gain insight into this mechanism of protection, we analyzed the expression profiles of NF90ctv-positive cells as compared with parental cells transduced with the empty vector. Of the 5600 genes represented on the expression arrays, 90 displayed significant (4-fold or more) changes in mRNA levels in NF90-expressing cells. About 50% are known interferon alpha/beta-stimulated genes. The microarray expression data were confirmed by quantitative reverse transcriptase-polymerase chain reaction analysis of six representative interferon-inducible genes. Electrophoretic mobility shift assays showed that the biological response is mediated by the activation of transcription factors in NF90ctv-expressing cells. Functional significance of the activated transcription complex was evaluated by transfection assays with luciferase reporter constructs driven by the interferon-inducible promoter from the 2'-5'-oligoadenylate synthetase (p69) gene. Resistance to HIV-1, caused by the expression of NF90ctv in the cell culture system, appears to be mediated in part by the induction of interferon response genes. This leads to a hypothesis as to the mechanism of action of NF90 in mediating endogenous antiviral responses. |
| Databáze: | OpenAIRE |
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