The Ras-Raf pathway is activated in human immunodeficiency virus-infected monocytes and participates in the activation of NF-kappa B

被引:41
作者
Folgueira, L
Algeciras, A
MacMorran, WS
Bren, GD
Paya, CV
机构
[1] MAYO CLIN & MAYO FDN,DIV EXPTL PATHOL,ROCHESTER,MN 55905
[2] MAYO CLIN & MAYO FDN,DIV INFECT DIS,ROCHESTER,MN 55905
[3] MAYO CLIN & MAYO FDN,DEPT IMMUNOL,ROCHESTER,MN 55905
关键词
D O I
10.1128/JVI.70.4.2332-2338.1996
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Persistent human immunodeficiency virus (HIV) infection of human monocytes and macrophages increases I kappa B alpha degradation, resulting in the activation of NF-kappa B, a key transcription factor in the regulation of the HIV long terminal repeat. The signal transduction pathways leading to NF-kappa B activation in cells of the monocytic lineage, especially those regulated by HIV infection, and their relevance in regulating viral persistence remain unknown. Both p21(ras) and its downstream Raf-1 kinase participate in the transduction of signals initiated from a variety of cell surface receptors aid in the regulation of transcription factors. We have studied whether the Ras-Raf pathway is functional and participates in HIV-mediated KF-kappa B activation in monocytic cells. Constitutively active p21(ras) (v-H-Ras) activates NF-kappa B-dependent transcription and induces the nuclear translocation of a bona fide p65/p50 heterodimer by targeting I kappa B alpha. In addition, the constitutively active form of Raf (Raf BXB) also increases the KF-kappa B-dependent transcriptional activity. Because of the similarity between HIV and Ras-Raf-induced NF-kappa B activation in monocytic cells, we nest tested whether HIV-induced NF-kappa B activation was mediated by the Ras-Raf signal transduction pathway. Negative dominant forms of both Ras (Ras N17) and Raf (Raf 301) decreased the HIV- but not lipopolysaccharide-dependent NF-kappa B activation in U937 cells. Moreover, Raf-1 kinase activity was greater in HIV-infected than uninfected monocytic cells in in vitro kinase assays. Altogether, these results indicate that the Ras-Raf pathway is upregulated in HIV monocytic cells and participates in the virus-induced activation of NF-kappa B.
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页码:2332 / 2338
页数:7
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