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PMID: 12663765 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Human cytomegalovirus activates inflammatory cytokine responses via CD14 and Toll-like receptor 2.

Journal of virology ·Vol. 77 ·No. 8 ·2003-04-00 ·Pages 4588-96

Compton T, Kurt-Jones EA, Boehme KW, Belko J, Latz E, Golenbock DT, Finberg RW

Abstract

Human cytomegalovirus (CMV) is a ubiquitous opportunistic pathogen that causes significant morbidity and mortality in immunocompromised people. An understanding of how CMV induces and circumvents host immunity is of critical importance in efforts to design effective therapeutics. It was recently discovered that mere cell contact by CMV particles leads to profound modulation of cellular gene expression, including induction of inflammatory cytokines and interferon-stimulated genes characteristic of innate immune detection. These findings suggest that a membrane receptor recognizes a CMV envelope protein(s), leading to innate immune activation. Here, we show that the pattern recognition receptors Toll-like receptor 2 (TLR2) and CD14 recognize CMV virions and trigger inflammatory cytokine production. Induction of inflammatory cytokines is mediated via TLR2-dependent activation of NF-kappa B. Since many of the pathological processes associated with CMV disease are facilitated or directly mediated by inflammatory cytokines, identification of the host membrane detection machinery may ultimately lead to improved therapeutics.

MeSH Terms
Animals Cell Line Cytokines/metabolism Cytomegalovirus/immunology,pathogenicity Drosophila Proteins Humans Inflammation/immunology Leukocytes, Mononuclear/immunology,metabolism,virology Lipopolysaccharide Receptors/metabolism Membrane Glycoproteins/metabolism Mice Mice, Inbred C57BL NF-kappa B/metabolism Receptors, Cell Surface/metabolism Toll-Like Receptor 2 Toll-Like Receptors
Chemicals
Cytokines Drosophila Proteins Lipopolysaccharide Receptors Membrane Glycoproteins NF-kappa B Receptors, Cell Surface TLR2 protein, human Toll-Like Receptor 2 Toll-Like Receptors
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Compton Teresa
McArdle Laboratory for Cancer Research, University of Wisconsin-Madison Medical School, Madison, Wisconsin 53706, USA. [email protected]
Kurt-Jones Evelyn A
Boehme Karl W
Belko John
Latz Eicke
Golenbock Douglas T
Finberg Robert W
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/jvi.77.8.4588-4596.2003
Email
[email protected]
Published
2003-04-00
Pages
4588-96
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC152130
Subset
IM
Grants
NIAID NIH HHS · R01 AI051405 · United States
NIAID NIH HHS · R01 AI049309 · United States
NIAID NIH HHS · AI 34998 · United States
NIGMS NIH HHS · T32 GM 072 15 · United States
NIGMS NIH HHS · GM 63244 · United States
NIAID NIH HHS · AI 49309 · United States
NIAID NIH HHS · R01 AI034998 · United States
NIAID NIH HHS · R21 AI034998 · United States
External Links
PubMed source DOI: 10.1128/jvi.77.8.4588-4596.2003 PMC Full Text View journal details
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