This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, T. S. Articles by Perlman, S. Search for Related Content PubMed PubMed Citation Articles by Kim, T. S. Articles by Perlman, S.

(American Journal of Pathology. 2005;166:801-809.)
© 2005 American Society for Investigative Pathology

Virus-Specific Antibody, in the Absence of T Cells, Mediates Demyelination in Mice Infected with a Neurotropic Coronavirus

Taeg S. Kim^* and Stanley Perlman^*

From the Interdisciplinary Program in Immunology^* and the Departments of Pediatrics and Microbiology, University of Iowa, Iowa City, Iowa

Mice infected with mouse hepatitis virus strain JHM develop an inflammatory demyelinating disease in the central nervous system with many similarities to human multiple sclerosis. The mouse disease is primarily immune-mediated because demyelination is not detected in JHM-infected mice lacking T or B cells but does occur after transfer of JHM-specific T cells. Although less is known about the ability of antibodies to mediate demyelination, the presence of oligoclonally expanded B cells and high concentrations of antibodies (against self or infectious agents) in the central nervous system of many multiple sclerosis patients suggests that antibodies may also contribute to myelin destruction. Here, we show that anti-JHM antibodies, in the absence of T or B cells, caused demyelination in JHM-infected mice. Anti-JHM antibody was detected adjacent to areas of demyelination, consistent with a direct interaction between antibody and infected cells. Demyelination was reduced by 85 to 90% in infected RAG1^–/– mice lacking normal expression of activating Fc receptors (FcR^–/–) and by 76% when complement was depleted by treatment with cobra venom factor. These data demonstrate that JHM-specific antibodies are sufficient to cause demyelination and that myelin destruction in the presence of anti-virus antibodies results from a combination of complement- and Fc receptor-dependent mechanisms.

This article has been cited by other articles:

				A. Khanolkar, S. M. Hartwig, B. A. Haag, D. K. Meyerholz, L. L. Epping, J. S. Haring, S. M. Varga, and J. T. Harty Protective and Pathologic Roles of the Immune Response to Mouse Hepatitis Virus Type 1: Implications for Severe Acute Respiratory Syndrome J. Virol., September 15, 2009; 83(18): 9258 - 9272. [Abstract] [Full Text] [PDF]

				J. Netland, D. K. Meyerholz, S. Moore, M. Cassell, and S. Perlman Severe Acute Respiratory Syndrome Coronavirus Infection Causes Neuronal Death in the Absence of Encephalitis in Mice Transgenic for Human ACE2 J. Virol., August 1, 2008; 82(15): 7264 - 7275. [Abstract] [Full Text] [PDF]

				R. A. Sobel Anti-Viral T-Cell Immunity + Anti-CNS Autoantibody = A Model for Human Acute Disseminated Encephalomyelitis or Multiple Sclerosis Relapse? Am. J. Pathol., February 1, 2007; 170(2): 436 - 438. [Full Text] [PDF]

				L. Pewe, H. Zhou, J. Netland, C. Tangudu, H. Olivares, L. Shi, D. Look, T. Gallagher, and S. Perlman A Severe Acute Respiratory Syndrome-Associated Coronavirus-Specific Protein Enhances Virulence of an Attenuated Murine Coronavirus J. Virol., September 1, 2005; 79(17): 11335 - 11342. [Abstract] [Full Text] [PDF]

				T. S. Kim and S. Perlman Viral Expression of CCL2 Is Sufficient To Induce Demyelination in RAG1-/- Mice Infected with a Neurotropic Coronavirus J. Virol., June 1, 2005; 79(11): 7113 - 7120. [Abstract] [Full Text] [PDF]