Insulin degrading enzyme induces a conformational change in varicella-zoster virus gE, and enhances virus infectivity and stability

Qingxue Li, Mir A. Ali, Kening Wang, Dean Sayre, Frederick G Hamel, Elizabeth R. Fischer, Robert G Bennett, Jeffrey I. Cohen

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Varicella-zoster virus (VZV) glycoprotein E (gE) is essential for virus infectivity and binds to a cellular receptor, insulindegrading enzyme (IDE), through its unique amino terminal extracellular domain. Previous work has shown IDE plays an important role in VZV infection and virus cell-to-cell spread, which is the sole route for VZV spread in vitro. Here we report that a recombinant soluble IDE (rIDE) enhances VZV infectivity at an early step of infection associated with an increase in virus internalization, and increases cell-to-cell spread. VZV mutants lacking the IDE binding domain of gE were impaired for syncytia formation and membrane fusion. Pre-treatment of cell-free VZV with rIDE markedly enhanced the stability of the virus over a range of conditions. rIDE interacted with gE to elicit a conformational change in gE and rendered it more susceptible to proteolysis. Co-incubation of rIDE with gE modified the size of gE. We propose that the conformational change in gE elicited by IDE enhances infectivity and stability of the virus and leads to increased fusogenicity during VZV infection. The ability of rIDE to enhance infectivity of cell-free VZV over a wide range of incubation times and temperatures suggests that rIDE may be useful for increasing the stability of varicella or zoster vaccines.

Original languageEnglish (US)
Article numbere11327
JournalPloS one
Volume5
Issue number6
DOIs
StatePublished - Aug 12 2010

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Insulysin
Human herpesvirus 3
Human Herpesvirus 3
Viruses
glycoproteins
Glycoproteins
insulin
pathogenicity
viruses
enzymes
Enzymes
Virus Diseases
cells
Herpes Zoster Vaccine
infection
Chickenpox Vaccine
Virus Internalization
Membrane Fusion
giant cells
Giant Cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Insulin degrading enzyme induces a conformational change in varicella-zoster virus gE, and enhances virus infectivity and stability. / Li, Qingxue; Ali, Mir A.; Wang, Kening; Sayre, Dean; Hamel, Frederick G; Fischer, Elizabeth R.; Bennett, Robert G; Cohen, Jeffrey I.

In: PloS one, Vol. 5, No. 6, e11327, 12.08.2010.

Research output: Contribution to journalArticle

Li, Qingxue ; Ali, Mir A. ; Wang, Kening ; Sayre, Dean ; Hamel, Frederick G ; Fischer, Elizabeth R. ; Bennett, Robert G ; Cohen, Jeffrey I. / Insulin degrading enzyme induces a conformational change in varicella-zoster virus gE, and enhances virus infectivity and stability. In: PloS one. 2010 ; Vol. 5, No. 6.
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