Insulin degrading enzyme is a cellular receptor mediating varicella-zoster virus infection and cell-to-cell spread.
Varicella-zoster virus (VZV) causes chickenpox and shingles. While varicella is likely spread as cell-free virus to susceptible hosts, the virus is transmitted by cell-to-cell spread in the body and in vitro. Since VZV glycoprotein E (gE) is essential for virus infection, we postulated that gE binds to a cellular receptor. We found that insulin-degrading enzyme (IDE) interacts with gE through its extracellular domain. Downregulation of IDE by siRNA, or blocking of IDE with antibody, with soluble IDE protein extracted from liver, or with bacitracin inhibited VZV infection. Cell-to-cell spread of virus was also impaired by blocking IDE. Transfection of cell lines impaired for VZV infection with a plasmid expressing human IDE resulted in increased entry and enhanced infection with cell-free and cell-associated virus. These studies indicate that IDE is a cellular receptor for both cell-free and cell-associated VZV.
Li
Qingxue
Q
Laboratory of Clinical Infectious Diseases, Medical Virology Section, National Institutes of Health, Bethesda, MD, 20892 USA.
Ali
Mir A
MA
Cohen
Jeffrey I
JI
D000818:Animals; D000891:Anti-Infective Agents, Local / Q000494:pharmacology; D000911:Antibodies, Monoclonal; D001414:Bacitracin / Q000494:pharmacology; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D006367:HeLa Cells; D006562:Herpes Zoster / Q000276:immunology / Q000378:metabolism / Q000821:virology; D014645:Herpesvirus 3, Human / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D007339:Insulysin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014162:Transfection; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism*; D014774:Virulence / Q000187:drug effects
D000891:Anti-Infective Agents, Local; D000911:Antibodies, Monoclonal; D034741:RNA, Small Interfering; D014759:Viral Envelope Proteins; C056913:glycoprotein E, varicella-zoster virus; D001414:Bacitracin; D007339:Insulysin