A role for dual viral hits in causation of subacute sclerosing panencephalitis.

Abstract

Subacute sclerosing panencephalitis (SSPE) is a progressive fatal neurodegenerative disease associated with persistent infection of the central nervous system (CNS) by measles virus (MV), biased hypermutations of the viral genome affecting primarily the matrix (M) gene with the conversion of U to C and A to G bases, high titers of antibodies to MV, and infiltration of B cells and T cells into the CNS. Neither the precipitating event nor biology underlying the MV infection is understood, nor is their any satisfactory treatment. We report the creation of a transgenic mouse model that mimics the cardinal features of SSPE. This was achieved by initially infecting mice expressing the MV receptor with lymphocytic choriomeningitis virus Cl 13, a virus that transiently suppressed their immune system. Infection by MV 10 days later resulted in persistent MV infection of neurons. Analysis of brains from infected mice showed the biased U to C hypermutations in the MV M gene and T and B lymphocyte infiltration. These sera contained high titers of antibodies to MV. Thus, a small animal model is now available to both molecularly probe the pathogenesis of SSPE and to test a variety of therapies to treat the disease.

• Authors: Michael B A Oldstone, Samuel Dales, Antoinette Tishon, Hanna Lewicki, Lee Martin
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 202 Issue 9 Pg. 1185-90 (Nov 07 2005) ISSN: 0022-1007 [Print] United States
• PMID: 16260490 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Homeodomain Proteins
• Mcp protein, mouse
• Membrane Cofactor Protein
• Receptors, Virus
• RAG-1 protein

Topics

• Animals
• Base Sequence
• Homeodomain Proteins (genetics)
• Lymphocytic choriomeningitis virus (immunology, pathogenicity)
• Measles virus (genetics, immunology, pathogenicity)
• Membrane Cofactor Protein (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Molecular Sequence Data
• Mutation
• Receptors, Virus (genetics, metabolism)
• Sequence Analysis, DNA
• Subacute Sclerosing Panencephalitis (immunology, virology)