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Attachment glycoproteins and receptor specificity of rat coronaviruses
S Gagneten1, C A Scanga, G S Dveksler
1Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Abstract:
Murine coronavirus (MHV) and rat coronavirus (RCV) are antigenically related viruses that have different natural rodent hosts. Both MHV and RCV can be propagated in the L2(Percy) and CMT-93 mouse cell lines. In these cell lines MHV uses the MHV receptor (MHVR or Bgp1a) and several related murine Bgp glycoproteins in the immunoglobulin superfamily as receptors. To determine whether RCV also uses these murine glycoproteins as receptors, we characterized the envelope glycoproteins of two strains of RCV and compared the effects of anti-MHVR monoclonal antibody on susceptibility of the mouse cells to MHV and RCV. The Parker (RCV-P) and sialodacryoadenitis (RCV-SDAV) strains of RCV expressed the spike glycoprotein S, but only RCV-P expressed a hemagglutinin-esterase glycoprotein that had acetylesterase activity. Therefore RCV-SDAV must bind to cellular receptors by the viral S glycoprotein, whereas RCV-P might bind to cells by its hemagglutinin-esterase glycoprotein as well as by S. Pretreatment of L2(Percy) 41.a or CMT-93 cells with anti-MHVR monoclonal antibody blocked infection with MHV-A59 but did not prevent infection of these murine cells with RCV-P or RCV-SDAV. Baby hamster kidney cells transfected with cDNAs encoding MHVR (Bgp1a) or Bgp2 were susceptible to MHV-A59 but not to RCV-P or RCV-SDAV. Thus the RCV strains cannot use these murine coronavirus receptors and must be infecting murine cells by another, as yet unknown, receptor.
Insights
Rat coronaviruses (RCV) do not use the same cellular receptors as murine coronaviruses (MHV) in mouse cells. This study found RCV infects mouse cells via an unknown receptor, distinct from the MHV receptor (MHVR).
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Murine coronavirus (MHV) and rat coronavirus (RCV) are related viruses with different natural hosts.
- MHV utilizes the murine beta-coronavirus receptor (MHVR) and related murine glycoproteins for cell entry.
- Both MHV and RCV can infect mouse cell lines, suggesting potential receptor overlap.
Purpose of the Study:
- To investigate whether RCV utilizes the same murine glycoproteins as receptors as MHV.
- To characterize RCV envelope glycoproteins and their role in cell binding.
- To determine the cellular receptor(s) used by RCV in mouse cell lines.
Main Methods:
- Characterization of envelope glycoproteins (spike and hemagglutinin-esterase) of RCV strains (RCV-P and RCV-SDAV).
- Treatment of mouse cell lines (L2(Percy) and CMT-93) with anti-MHVR monoclonal antibody.
- Infection assays using MHV and RCV strains on untreated and antibody-treated cells.
- Transfection of baby hamster kidney cells with cDNAs encoding MHVR (Bgp1a) or Bgp2 for susceptibility testing.
Main Results:
- RCV-SDAV expressed only the spike (S) glycoprotein, while RCV-P expressed both S and hemagglutinin-esterase (HE) glycoproteins.
- Anti-MHVR antibody blocked MHV-A59 infection but did not affect RCV-P or RCV-SDAV infection in mouse cells.
- MHVR-transfected cells were susceptible to MHV-A59 but not to RCV-P or RCV-SDAV.
Conclusions:
- RCV strains cannot use the known murine coronavirus receptors (MHVR and related Bgp glycoproteins).
- RCV likely infects murine cells using a distinct, currently unidentified cellular receptor.
- This finding highlights differences in host-pathogen interactions and viral entry mechanisms between related coronaviruses.