N-terminal domain of the murine coronavirus receptor CEACAM1 is responsible for fusogenic activation and conformational changes of the spike protein

J Virol. 2004 Jan;78(1):216-23. doi: 10.1128/jvi.78.1.216-223.2004.


The mouse hepatitis virus (MHV) receptor (MHVR), CEACAM1, has two different functions for MHV entry into cells: binding to MHV spike protein (S protein) and activation of the S protein to execute virus-cell membrane fusion, the latter of which is accompanied by conformational changes of the S protein. The MHVR comprising the N-terminal and fourth domains [R1(1,4)] displays these two activities, and the N domain is thought to be critical for binding to MHV. In this study, we have addressed whether or not the N domain alone is sufficient for these activities. We examined three types of soluble form MHVR (soMHVR), one consisting of the N domain alone [soR1(1)], one with the N and second domains [soR1(1,2)], and one [soR1(1,4)] expressed by recombinant baculoviruses. We assessed the abilities of these three types of soMHVR to bind to MHV, activate fusogenicity, and induce conformational changes of the S protein. All three types of soMHVR similarly bound to MHV, as examined by a solid-phase binding assay and neutralized MHV infectivity. They also activated S protein fusogenicity and induced its conformational changes with similar levels of efficiency. However, R1(1) expressed on the BHK cell surface failed to serve as a receptor in spite of a sufficient level of expression. The inability of expressed R1(1) to work as a receptor was due to the inaccessibility of virions to R1(1); however, these were accessible using the MHVR-specific monoclonal antibody CC1. These results collectively indicated that the N domain retains all biological activities necessary for receptor function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / chemistry*
  • Antigens, CD / metabolism
  • Antigens, Differentiation / chemistry*
  • Antigens, Differentiation / metabolism
  • Carcinoembryonic Antigen
  • Cell Adhesion Molecules
  • Cell Line
  • Cell Membrane / metabolism
  • Cricetinae
  • Flow Cytometry
  • Membrane Fusion*
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / metabolism*
  • Murine hepatitis virus / metabolism
  • Murine hepatitis virus / pathogenicity*
  • Murine hepatitis virus / physiology
  • Neutralization Tests
  • Protein Conformation
  • Receptors, Virus / chemistry*
  • Receptors, Virus / metabolism
  • Spike Glycoprotein, Coronavirus
  • Structure-Activity Relationship
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / metabolism*


  • Antigens, CD
  • Antigens, Differentiation
  • CD66 antigens
  • Carcinoembryonic Antigen
  • Ceacam1 protein, mouse
  • Cell Adhesion Molecules
  • Membrane Glycoproteins
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins
  • spike glycoprotein, SARS-CoV
  • spike protein, mouse hepatitis virus