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The glycoprotein B disintegrin-like domain binds beta 1 integrin to mediate cytomegalovirus entry

Adam L Feire1, René M Roy, Kate Manley

  • 1McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, Wisconsin 53706, USA.

Journal of Virology
|July 28, 2010
PubMed

Insights

Human cytomegalovirus (HCMV) uses its glycoprotein B (gB) to bind cellular integrins, mimicking ADAM proteins. This interaction is key for virus entry and offers a novel therapeutic target for HCMV infection.

Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • Cellular integrins mediate human cytomegalovirus (HCMV) entry and signaling in fibroblasts and endothelial cells.
  • HCMV entry mechanisms are crucial for understanding viral pathogenesis and developing antiviral strategies.

Purpose of the Study:

  • To elucidate the mechanism of HCMV binding to cellular integrins for virus entry.
  • To investigate the role of HCMV glycoprotein B (gB) in integrin engagement.

Main Methods:

  • Generated a recombinant soluble gB disintegrin-like domain (gB-DLD) protein.
  • Assessed gB-DLD binding to human fibroblasts and its dependence on beta1 integrin.
  • Performed in vitro pull-down assays to demonstrate physical association between gB-DLD and beta1 integrin.
  • Evaluated the ability of gB-DLD to block HCMV entry and infectivity.
  • Generated antibodies against gB-DLD to test for HCMV neutralization.

Main Results:

  • gB-DLD bound specifically, dose-dependently, and saturably to fibroblasts, requiring intact beta1 integrin.
  • A physical association between gB-DLD and beta1 integrin was confirmed.
  • Cell-bound gB-DLD effectively blocked HCMV entry and infectivity in target cells.
  • Antibodies against gB-DLD neutralized HCMV infection.

Conclusions:

  • HCMV gB mimics the ADAM protein disintegrin-like domain to engage cellular integrins, a novel viral entry mechanism.
  • This gB-integrin interaction represents a potential therapeutic target for HCMV neutralization.
  • Conserved gB domains suggest integrin recognition is a broad feature across herpesviruses.

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