Transcription and translation of proinflammatory cytokines following JHMV infection.
Infection with JHMV results in the transcriptional activation of two host cell genes encoding proinflammatory cytokines, tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta. Analysis of irradiated mice showed that IL-1 beta mRNA accumulation in the central nervous system was predominantly derived from the mononuclear infiltrate. By contrast, accumulation of TNF-alpha mRNA was unaffected by immunosuppression, suggesting that resident cells were the source of this cytokine. Infected mice were treated with anti-TNF antibody to determine if TNF-alpha contributed to either the encephalomyelitis or demyelination associated with JHMV infection. Surprisingly, neither the cellular infiltrate nor demyelination were affected. In vitro analysis showed that IL-1 beta but not TNF was secreted from JHMV infected macrophages. The absence of TNF secretion is due to a block in translation of the TNF mRNA which accumulates during infection.
Stohlman
S A
SA
Department of Microbiology, University of Southern California, Los Angeles, USA.
Yao
Q
Q
Bergmann
C C
CC
Tahara
S M
SM
Kyuwa
S
S
Hinton
D R
DR
D000818:Animals; D001921:Brain / Q000276:immunology / Q000821:virology*; D002478:Cells, Cultured; D018352:Coronavirus Infections / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D003711:Demyelinating Diseases / Q000276:immunology / Q000473:pathology / Q000821:virology; D004679:Encephalomyelitis / Q000276:immunology / Q000473:pathology / Q000821:virology; D015967:Gene Expression Regulation, Viral; D007375:Interleukin-1 / Q000096:biosynthesis*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D006517:Murine hepatitis virus; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha