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Proteoglycans in host–pathogen interactions: molecular mechanisms and therapeutic implications

Published online by Cambridge University Press:  01 February 2010

Allison H. Bartlett
Affiliation:
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Pyong Woo Park*
Affiliation:
Division of Respiratory Diseases, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
*
*Corresponding author: Pyong Woo Park, Division of Respiratory Diseases, Children's Hospital, 320 Longwood Avenue, Enders-461, Boston, MA 02115, USA. E-mail: pyong.park@childrens.harvard.edu

Abstract

Many microbial pathogens subvert proteoglycans for their adhesion to host tissues, invasion of host cells, infection of neighbouring cells, dissemination into the systemic circulation, and evasion of host defence mechanisms. Where studied, specific virulence factors mediate these proteoglycan–pathogen interactions, which are thus thought to affect the onset, progression and outcome of infection. Proteoglycans are composites of glycosaminoglycan (GAG) chains attached covalently to specific core proteins. Proteoglycans are expressed ubiquitously on the cell surface, in intracellular compartments, and in the extracellular matrix. GAGs mediate the majority of ligand-binding activities of proteoglycans, and many microbial pathogens elaborate cell-surface and secreted factors that interact with GAGs. Some pathogens also modulate the expression and function of proteoglycans through known virulence factors. Several GAG-binding pathogens can no longer attach to and invade host cells whose GAG expression has been reduced by mutagenesis or enzymatic treatment. Furthermore, GAG antagonists have been shown to inhibit microbial attachment and host cell entry in vitro and reduce virulence in vivo. Together, these observations underscore the biological significance of proteoglycan–pathogen interactions in infectious diseases.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2010

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References

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Further reading, resources and contacts

Shukla, D. et al. (1999) A novel role for 3-O-sulfated heparan sulfate in herpes simplex virus 1 entry. Cell 99, 13-22Google Scholar
Reeves, E.P. et al. (2002) Killing activity of neutrophils is mediated through activation of proteases by K+ flux. Nature 416, 291-297Google Scholar
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Vivès, R.R., Lortat-Jacob, H. and Fender, P. (2006) Heparan sulphate proteoglycans and viral vectors: ally or foe? Current Gene Therapy 6, 35-44Google Scholar