Herpes simplex virus: discovering the link between heparan sulphate and hereditary bone tumours.
To gain entry into the host, viruses use host cell surface molecules that normally serve as receptors for other ligands. Herpes simplex virus type 1 (HSV-1) uses heparan sulphate (HS) glycosaminoglycans (GAGs) as receptors for initial attachment to the host cell surface. HS GAGs are both ubiquitous and structurally diverse, and normally serve as critical mediators of interactions between the cell and the extracellular environment. We have used the HS binding ability of HSV-1 to identify the function of a cellular gene, EXT1, which is involved in HS polymerisation. Cellular factors that affect virus growth and replication are often key regulators of the cell cycle and EXT1 is no different-humans with inherited mutations in EXT1 have developmental defects that lead to bone tumours (hereditary multiple exostoses, HME) and sometimes chondrosarcomas. Thus, as a result of using HSV-1 as a molecular probe, a functionally orphaned disease gene now has a defined function. These findings highlight the utility of viruses for investigating important cellular processes.
McCormick
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C
Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada V6T 1Z3.
Duncan
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G
Tufaro
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F
D002460:Cell Line; D005097:Exostoses, Multiple Hereditary / Q000209:etiology / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006497:Heparan Sulfate / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D015335:Molecular Probes; D009154:Mutation; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics; D014779:Virus Replication; D000099058:Exostosin 1
D006497:Heparan Sulfate; D015335:Molecular Probes; D017351:N-Acetylglucosaminyltransferases; D000099058:Exostosin 1