Spike glycoprotein-mediated fusion in biliary glycoprotein-independent cell-associated spread of mouse hepatitis virus infection.
The mouse hepatitis virus (MHV) spike glycoprotein mediates attachment of the virus to the MHV receptor, the murine biliary glycoprotein (BGP) carcinoembryonic antigen. Monoclonal antibody CC1 directed against BGP specifically inhibited infection of DBT, Sac-, GT1-7, and OBL21 cells by wild-type MHV-4 and the neuron-adapted variant OBLV60. Binding to this receptor was necessary to establish infection by cell-free MHV; however, the presence of BGP was not required for infection by cell-associated virus. Cell-associated infectious induced syncytium formation on Vero and BHK cells, which lack murine BGP; this activity was not inhibited by monoclonal antibody CC1. Antibody CC1 also did not prevent syncytium formation on DBT cells, which bear BGP. In infectious center assays, the MHV-4 variant OBLV60, which exhibits acid-dependent fusion, spread to cells lacking BGP only when exposed to acidic media. Therefore, spike-mediated fusion was required for BGP-independent spread of MHV infection. Furthermore, BGP-independent, cell-associated spread of MHV-4 was prevented by monoclonal antibodies 5A13.5 and 5B19.2 directed against the spike glycoprotein, but not by other neutralizing and nonneutralizing anti-spike antibodies. Expression of spike glycoprotein by recombinant vaccinia virus resulted in fusion of BGP-negative cells; monoclonal antibodies 5A13.5 and 5B19.2 strongly inhibited spike-mediated fusion in this assay.
Nash
T C
TC
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
Buchmeier
M J
MJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000276:immunology / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D002460:Cell Line; D006224:Cricetinae; D006023:Glycoproteins / Q000378:metabolism*; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D006517:Murine hepatitis virus / Q000378:metabolism* / Q000472:pathogenicity; D011991:Receptors, Virus / Q000378:metabolism*; D064370:Spike Glycoprotein, Coronavirus; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D002272:Carcinoembryonic Antigen; C087701:Ceacam2 protein, mouse; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins