title: Pathogenesis of neurotropic murine coronavirus is multifactorial.
abstract: Although coronavirus tropism is most often ascribed to receptor availability, increasing evidence suggests that for the neurotropic strains of the murine coronavirus mouse hepatitis virus (MHV), spike-receptor interactions cannot fully explain neurovirulence. The canonical MHV receptor CEACAM1a and its spike-binding site have been extensively characterized. However, CEACAM1a is poorly expressed in neurons, and the extremely neurotropic MHV strain JHM.SD infects ceacam1a(-/-) mice and spreads among ceacam1a(-/-) neurons. Two proposed alternative MHV receptors, CEACAM2 and PSG16, also fail to account for neuronal spread of JHM.SD in the absence of CEACAM1a. It has been reported that JHM.SD has an unusually labile spike protein, enabling it to perform receptor-independent spread (RIS), but it is not clear if the ability to perform RIS is fully responsible for the extremely neurovirulent phenotype. We propose that the extreme neurovirulence of JHM.SD is multifactorial and might include as yet unidentified neuron-specific spread mechanisms.
authors.affiliation: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6076, USA.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Phillips
authors.forename: Susan R
authors.initials: SR
authors.lastname: Weiss
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000821:virology; D002272:Carcinoembryonic Antigen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules; D018792:Encephalitis, Viral / Q000821:virology*; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D006517:Murine hepatitis virus / Q000378:metabolism / Q000472:pathogenicity*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000821:virology; D011257:Pregnancy Proteins / Q000737:chemistry / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D000085064:Receptors, Coronavirus; D011991:Receptors, Virus / Q000378:metabolism; D016415:Sequence Alignment; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000378:metabolism; D014774:Virulence
chemical_list: D002272:Carcinoembryonic Antigen; C486183:Ceacam1 protein, mouse; C087701:Ceacam2 protein, mouse; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C509693:PSG16 protein, mouse; D011257:Pregnancy Proteins; D020033:Protein Isoforms; D000085064:Receptors, Coronavirus; D011991:Receptors, Virus; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins