Species B adenovirus serotypes 3, 7, 11 and 35 share similar binding sites on the membrane cofactor protein CD46

Christoph Fleischli1, Dominique Sirena1, Guillaume Lesage1

  • 1Institute of Molecular Biology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.

Insights

Species B1 and B2 adenoviruses (Ads) bind to human CD46 using similar surface domains. This study maps the specific CD46 binding sites for Ad serotypes 3, 7, and 11, revealing conserved interactions.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Human cofactor protein CD46 serves as a receptor for certain adenovirus (Ad) serotypes.
  • Previous studies characterized CD46 binding for species B2 Ad serotype 35.

Purpose of the Study:

  • To map the CD46 binding determinants for species B1 Ad serotypes 3 and 7, and species B2 Ad11.
  • To compare the CD46 binding mechanisms of different adenovirus species.

Main Methods:

  • Antibody-blocking experiments were employed to identify binding sites.
  • Hybrid CD46-CD4 receptor constructs were utilized to analyze domain interactions.
  • Single point mutations in CD46 were generated to pinpoint critical binding residues.
  • Competition experiments with anti-CD46 antibodies and soluble CD46 protein were performed.

Main Results:

  • Adenovirus serotypes 3, 7, and 11 bound and transduced CD46-positive cells similarly to Ad35.
  • Both CD46 short consensus repeat domains (SCR I and SCR II) were essential and sufficient for optimal Ad binding and transgene expression.
  • Putative binding residues for Ad3, 7, and 11 were located on a similar face of SCR I or SCR II, overlapping with the Ad11-CD46 structure.
  • Differences in binding between species B1 and B2 Ads were observed through competition assays.

Conclusions:

  • Species B1 and B2 adenoviruses engage CD46 through largely conserved binding surfaces.
  • The SCR I and SCR II domains of CD46 are critical for binding multiple adenovirus serotypes.
  • Structural and functional similarities exist in CD46-adenovirus interactions across different species.

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