Requirements for the induction of interleukin-6 by herpes simplex virus-infected leukocytes.
J Virol
; 75(17): 8008-15, 2001 Sep.
Article
em En
| MEDLINE
| ID: mdl-11483745
ABSTRACT
Cytokines play important roles in the clearance of herpes simplex virus (HSV) infections and in virus-induced immunopathology. One cytokine known to contribute to resistance against HSV is interleukin-6 (IL-6). Here we have investigated virus-cell interactions responsible for IL-6 induction by HSV in leukocytes. Both HSV type 1 and type 2 are potent inducers of IL-6, and this phenomenon is augmented in the presence of gamma interferon. The ability to induce IL-6 is dependent on de novo protein synthesis and is sensitive to UV irradiation of the virus. Virus mutants lacking the virion-transactivating protein VP16 or any of the immediate-early proteins ICP0, ICP4, or ICP27 displayed unaltered capacities to induce IL-6. However, wild-type virus was unable to induce IL-6 in a macrophage cell line overexpressing a mutant of double-stranded RNA-activated protein kinase (PKR). This suggests a role for PKR in HSV-induced IL-6 expression. HSV infection led to enhanced binding to the kappaB, CRE, and AP-1 sites of the IL-6 promoter, and inhibitors against NF-kappaB and the p38 kinase strongly reduced accumulation of IL-6 mRNA in infected cells. Moreover, macrophage cell lines expressing dominant negative mutants of IkappaBalpha and p38 responded to HSV-1 infection with reduced IL-6 expression compared to the control-vector-transfected cell line. The results show that induction of IL-6 by HSV in leukocytes is dependent on PKR and cellular signaling through NF-kappaB and a p38-dependent pathway.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucócitos Mononucleares
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Interleucina-6
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Herpesvirus Humano 2
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Herpesvirus Humano 1
Limite:
Adult
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Animals
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Humans
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Male
Idioma:
En
Revista:
J Virol
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Dinamarca