Accumulated evidence suggests that the E2 spike protein of the murine coronaviruses contains domains which are important in virus attachment and neutralization, and in mediating cell to cell fusion. We have recently shown that variants of MHV-JHM selected in this laboratory (MHV-4) contain lesions in the E2 protein which render them resistant to neutralizing monoclonal antibodies and are attenuated in their neurovirulence. Infections by these variant viruses are restricted predominantly to CNS glial cells, in vivo, and result in chronic demyelinating disease characterized by episodes of demyelination, remyelination, and further demyelination accompanied by mild mononuclear cell inflammatory responses. We propose to study several aspects of the specificity of this neurovirulence by analyzing these E2 mutants at the molecular level using RNA and protein sequencing, by analyzing CNS neurons for the presence of virus specific receptors using anti- idiotypic antibodies against defined monoclonals, and by studying the significance of sequence homologies observed between MHV- JHM E2 glycoprotein and normal tissue constituents such as myelin basic protein and fibronectins. These studies will contribute to our understanding of the events and/or molecules which govern the fate of viral infections of the CNS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI025913-02
Application #
3139600
Study Section
Virology Study Section (VR)
Project Start
1988-02-01
Project End
1991-01-31
Budget Start
1989-02-01
Budget End
1990-01-31
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
San Diego
State
CA
Country
United States
Zip Code
92037
Neuman, Benjamin W; Kiss, Gabriella; Kunding, Andreas H et al. (2011) A structural analysis of M protein in coronavirus assembly and morphology. J Struct Biol 174:11-22
Burrer, Renaud; Buchmeier, Michael J; Wolfe, Tom et al. (2007) Exacerbated pathology of viral encephalitis in mice with central nervous system-specific autoantibodies. Am J Pathol 170:557-66
Burrer, Renaud; Neuman, Benjamin W; Ting, Joey P C et al. (2007) Antiviral effects of antisense morpholino oligomers in murine coronavirus infection models. J Virol 81:5637-48
Neuman, Benjamin W; Stein, David A; Kroeker, Andrew D et al. (2006) Inhibition and escape of SARS-CoV treated with antisense morpholino oligomers. Adv Exp Med Biol 581:567-71
Neuman, Benjamin W; Adair, Brian D; Yoshioka, Craig et al. (2006) Ultrastructure of SARS-CoV, FIPV, and MHV revealed by electron cryomicroscopy. Adv Exp Med Biol 581:181-5
Burrer, Renaud; von Herrath, Matthias G; Wolfe, Tom et al. (2006) Autoantibodies exacerbate the severity of MHV-induced encephalitis. Adv Exp Med Biol 581:399-402
Neuman, Benjamin W; Adair, Brian D; Yoshioka, Craig et al. (2006) Supramolecular architecture of severe acute respiratory syndrome coronavirus revealed by electron cryomicroscopy. J Virol 80:7918-28
Rempel, J D; Quina, L A; Blakely-Gonzales, P K et al. (2005) Viral induction of central nervous system innate immune responses. J Virol 79:4369-81
Sampath, Rangarajan; Hofstadler, Steven A; Blyn, Lawrence B et al. (2005) Rapid identification of emerging pathogens: coronavirus. Emerg Infect Dis 11:373-9
Neuman, Benjamin W; Stein, David A; Kroeker, Andrew D et al. (2005) Inhibition, escape, and attenuated growth of severe acute respiratory syndrome coronavirus treated with antisense morpholino oligomers. J Virol 79:9665-76

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