Abstract

This proposal brings together a group of investigators with expertise in different viral systems and centers around the common theme of interactions of viruses with the nervous system. The overall goal is a better understanding of the relationships between viral proteins and the determinants of neural cell differentiation, particularly as they relate to viral tropism and viral pathology. The proposal contains 5 major components: 4 projects and 1 core. In project I, Dr. Gonzalez-Scarano will look at the interaction of two HIV viral proteins with neural cells and neural cell components; in project II, Dr. Gaulton will study the neuropathology of Gross murine leukemia virus; in project III, Dr. Weiss will study the cytopathology of murine coronaviruses in neural cells, with particular emphasis on the fusion process; in project IV Drs. Eisenberg and Cohen will identify the receptor molecule(s) responsible for Herpes Simplex entry into nervous system cells. Dr. Pleasure will direct a cell culture core that will provide specialized cells and analytical expertise to all of the component projects. The findings from each of these component projects will enhance our understanding of neurologic dysfunction mediated by viruses, and will have applicability to the study of multiple sclerosis, viral encephalitis and AIDS.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS030606-02
Application #
2268576
Study Section
Neurological Disorders Program Project Review B Committee (NSPB)
Project Start
1993-01-01
Project End
1997-12-31
Budget Start
1994-01-01
Budget End
1994-12-31
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Neurology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Plassmeyer, Matthew L; Soldan, Samantha S; Stachelek, Karen M et al. (2007) Mutagenesis of the La Crosse Virus glycoprotein supports a role for Gc (1066-1087) as the fusion peptide. Virology 358:273-82
Murphy, Samuel L; Chung-Landers, Maeran; Honczarenko, Marek et al. (2006) Linkage of reduced receptor affinity and superinfection to pathogenesis of TR1.3 murine leukemia virus. J Virol 80:4601-9
Simpson, Scott A; Manchak, Michael D; Hager, Elizabeth J et al. (2005) Nectin-1/HveC Mediates herpes simplex virus type 1 entry into primary human sensory neurons and fibroblasts. J Neurovirol 11:208-18
MacNamara, Katherine C; Chua, Ming Ming; Nelson, Peter T et al. (2005) Increased epitope-specific CD8+ T cells prevent murine coronavirus spread to the spinal cord and subsequent demyelination. J Virol 79:3370-81
Soldan, Samantha S; Plassmeyer, Matthew L; Matukonis, Meghan K et al. (2005) La Crosse virus nonstructural protein NSs counteracts the effects of short interfering RNA. J Virol 79:234-44
Weiss, Susan R; Navas-Martin, Sonia (2005) Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus. Microbiol Mol Biol Rev 69:635-64
Plassmeyer, Matthew L; Soldan, Samantha S; Stachelek, Karen M et al. (2005) California serogroup Gc (G1) glycoprotein is the principal determinant of pH-dependent cell fusion and entry. Virology 338:121-32
Navas-Martin, Sonia R; Weiss, Susan (2004) Coronavirus replication and pathogenesis: Implications for the recent outbreak of severe acute respiratory syndrome (SARS), and the challenge for vaccine development. J Neurovirol 10:75-85
Fu, Li; Gonzales, Donna M; Das Sarma, Jayasri et al. (2004) A combination of mutations in the S1 part of the spike glycoprotein gene of coronavirus MHV-A59 abolishes demyelination. J Neurovirol 10:41-51
Landers, Maeran Chung; Dugger, Natalie; Quadros, Marlene et al. (2004) Neuropathogenic murine leukemia virus TR1.3 induces selective syncytia formation of brain capillary endothelium. Virology 321:57-64

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