Impact of RNase L overexpression on viral and cellular growth and death.
J Interferon Cytokine Res
; 18(11): 953-61, 1998 Nov.
Article
em En
| MEDLINE
| ID: mdl-9858317
ABSTRACT
The biologic actions of interferons (IFNs) are complex and involve multiple biochemical mechanisms, including the 2-5A system, a regulated RNA decay pathway. The 2-5A system is implicated in the antipicornavirus activity of IFN and in the control of apoptosis. To further investigate involvement of the 2-5A system in the control of viral and cellular growth and death, human RNase L cDNA was stably expressed in murine 3T3 cells from a constitutive cytomegalovirus (CMV) promoter. A clonal cell line, 3T3/pLZ, was isolated that overexpressed RNase L by >100-fold compared with levels of the endogenous murine RNase L. Interestingly, human RNase L levels in 3T3/pLZ cells decreased 3-fold as cells entered a confluent, growth arrest state, suggesting autoregulation. Overexpression of human RNase L greatly enhanced both the cell growth inhibitory activity of IFN and the proapoptotic activity of staurosporine. Furthermore, high levels of RNase L suppressed the replication of diverse viruses encephalomyocarditis virus, vesicular stomatitis virus, human parainfluenza virus-3, and vaccinia virus. Additional reductions in viral growth were obtained by treating 3T3/pLZ cells with IFN (a + beta) before infections. These results directly demonstrate the anticellular and antiviral potential of the 2-5A system.
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Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Oligorribonucleotídeos
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Inibidores da Síntese de Proteínas
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Nucleotídeos de Adenina
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Regulação Enzimológica da Expressão Gênica
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Endorribonucleases
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
1998
Tipo de documento:
Article