Document Detail

Robust expression of TNF-alpha, IL-1beta, RANTES, and IP-10 by human microglial cells during nonproductive infection with herpes simplex virus.
MedLine Citation:
PMID:  11517395     Owner:  NLM     Status:  MEDLINE    
Cytokine (TNF-alpha/beta, IL-1beta, IL-6, IL-18, IL-10, and IFN-alpha/beta/gamma) and chemokine (IL-8, IP-10, MCP-1, MIP-1alpha/beta, and RANTES) production during herpes simplex virus (HSV) 1 infection of human brain cells was examined. Primary astrocytes as well as neurons were found to support HSV replication, but neither of these fully permissive cell types produced cytokines or chemokines in response to HSV. In contrast, microglia did not support extensive viral replication; however, ICP4 was detected by immunochemical staining, demonstrating these cells were infected. Late viral protein (nucleocapsid antigen) was detected in <10% of infected microglial cells. Microglia responded to nonpermissive viral infection by producing considerable amounts of TNF-alpha, IL-1beta, IP-10, and RANTES, together with smaller amounts of IL-6, IL-8, and MIP-1alpha as detected by RPA and ELISA. Surprisingly, no interferons (alpha, beta, or gamma) were detected in response to viral infection. Pretreatment of fully permissive astrocytes with TNF-alpha prior to infection with HSV was found to dramatically inhibit replication, resulting in a 14-fold reduction of viral titer. In contrast, pretreatment of astrocytes with IL-1beta had little effect on viral replication. When added to neuronal cultures, exogenous TNF-alpha or IL-1beta did not suppress subsequent HSV replication. Exogenously added IP-10 inhibited HSV replication in neurons (with a 32-fold reduction in viral titer), however, similar IP-10 treatment did not affect viral replication in astrocytes. These results suggest that IP-10 possesses direct antiviral activity in neurons and support a role for microglia in both antiviral defense of the brain as well as amplification of immune responses during neuroinflammation.
J R Lokensgard; S Hu; W Sheng; M vanOijen; D Cox; M C Cheeran; P K Peterson
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neurovirology     Volume:  7     ISSN:  1355-0284     ISO Abbreviation:  J. Neurovirol.     Publication Date:  2001 Jun 
Date Detail:
Created Date:  2001-08-22     Completed Date:  2001-09-20     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9508123     Medline TA:  J Neurovirol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  208-19     Citation Subset:  IM    
Neuroimmunology Laboratory, Minneapolis Medical Research Foundation, Minneapolis, Minnesota 55404, USA.
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MeSH Terms
Astrocytes / cytology,  virology
Brain / cytology,  virology
Butadienes / pharmacology
Cell Death / immunology
Cells, Cultured
Chemokine CCL5 / biosynthesis,  immunology
Chemokine CXCL10
Chemokines, CXC / biosynthesis,  immunology
Cytokines / biosynthesis,  immunology*
Encephalitis, Herpes Simplex / immunology*
Enzyme Inhibitors / pharmacology
Fetus / cytology
Herpesvirus 1, Human / growth & development*
Imidazoles / pharmacology
Interleukin-1 / biosynthesis,  immunology
Microglia / cytology,  metabolism,  virology*
Neurons / cytology,  virology
Nitriles / pharmacology
Pyridines / pharmacology
Signal Transduction / drug effects,  immunology
Tumor Necrosis Factor-alpha / biosynthesis,  immunology
Virus Replication
Grant Support
Reg. No./Substance:
0/4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; 0/Butadienes; 0/Chemokine CCL5; 0/Chemokine CXCL10; 0/Chemokines, CXC; 0/Cytokines; 0/Enzyme Inhibitors; 0/Imidazoles; 0/Interleukin-1; 0/Nitriles; 0/Pyridines; 0/Tumor Necrosis Factor-alpha; 0/U 0126

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